Sonia Melgar-Locatelli1,2†Marialuisa de Ceglia1,3†M. Carmen Mañas-Padilla1,2
Celia Rodriguez-Pérez4,5,6
Estela Castilla-Ortega1,2*
Adriana Castro-Zavala1,2*
Patricia Rivera1,3*- 1Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND, Málaga, Spain
- 2Departamento de Psicobiología y Metodología de las Ciencias del Comportamiento, Facultad de Psicología, Universidad de Málaga, Málaga, Spain
- 3UGC Salud Mental, Hospital Universitario Regional de Málaga, Málaga, Spain
- 4Departamento de Nutrición y Bromatología, Facultad de Ciencias de la Salud, Universidad de Granada, Granada, Spain
- 5Instituto de Nutrición y Tecnología de los Alimentos ‘José Mataix’, Universidad de Granada, Granada, Spain
- 6Instituto de Investigación Biosanitaria ibs.GRANADA, Granada, Spain
Neurogenesis is a complex process by which neural progenitor cells (NPCs)/neural stem cells (NSCs) proliferate and differentiate into new neurons and other brain cells. In adulthood, the hippocampus is one of the areas with more neurogenesis activity, which is involved in the modulation of both emotional and cognitive hippocampal functions. This complex process is affected by many intrinsic and extrinsic factors, including nutrition. In this regard, preclinical studies performed in rats and mice demonstrate that high fats and/or sugars diets have a negative effect on adult hippocampal neurogenesis (AHN). In contrast, diets enriched with bioactive compounds, such as polyunsaturated fatty acids and polyphenols, as well as intermittent fasting or caloric restriction, can induce AHN. Interestingly, there is also growing evidence demonstrating that offspring AHN can be affected by maternal nutrition in the perinatal period. Therefore, nutritional interventions from early stages and throughout life are a promising perspective to alleviate neurodegenerative diseases by stimulating neurogenesis. The underlying mechanisms by which nutrients and dietary factors affect AHN are still being studied. Interestingly, recent evidence suggests that additional peripheral mediators may be involved. In this sense, the microbiota-gut-brain axis mediates bidirectional communication between the gut and the brain and could act as a link between nutritional factors and AHN. The aim of this mini-review is to summarize, the most recent findings related to the influence of nutrition and diet in the modulation of AHN. The importance of maternal nutrition in the AHN of the offspring and the role of the microbiota-gut-brain axis in the nutrition-neurogenesis relationship have also been included.
1. Introduction
Hippocampus, a region extensively known to regulate learning, memory, and mood can be found among the highly sensitive, environment-responsive structures of the brain (Squire, 1992; Clelland et al., 2009; Castilla-Ortega et al., 2011; Murphy et al., 2014). The hippocampus is one of the main structures in the adult brain where the formation of new-born neurons, or neurogenesis, persists all lifelong (Eriksson et al., 1998). In this regard, the birth and maturation of neurons in the dentate gyrus of the adult hippocampus, known as adult hippocampal neurogenesis (AHN), is one of the most studied neuroplastic phenomena. Research in rodents supports a relevant role of AHN in the adaptation to environmental demands. For example, AHN facilitates a variety of cognitive functions including the long-term consolidation of new hippocampal memories -as well as the forgetting of previously acquired ones- and it is also involved in emotional regulation such as in providing stress resilience [reviewed in Wu et al. (2021)]. Accordingly, manipulations of AHN have functional consequences as they usually correlate with changes in memory and mood (Castilla-Ortega et al., 2011; Yau et al., 2015).
The plasticity of these new hippocampal neurons is greater than those of adult neurons. They exhibit a lower threshold for induction of long-term potentiation (LTP), possibly because new neurons can depolarize using currents of very small amplitude (Wang et al., 2000; Schmidt-Hieber et al., 2004). In addition, they are able to more rapidly form branches and synapses (Gould and Gross, 2002), so the plasticity of these new neurons is greater than those of more adult neurons. From 3-4 weeks of age the new neurons show similar properties to the older granular neurons that compose the cell layer of the dentate gyrus. This plasticity and excitability exhibited by new hippocampal neurons seem to contribute to explain the important role of the NHA in hippocampal-dependent learning and memory, such as spatial learning or complex associative learning (Leuner et al., 2006; Kee et al., 2007; Koehl and Abrous, 2011). Therefore, the processes of proliferation, survival, maturation, and functional integration of the new hippocampal neurons critically depend on intrinsic and extrinsic factors. Thus, aging, neuroinflammation, oxidative stress and brain injury, as well as exposure to drugs of abuse such as alcohol and opiates, negatively affect adult neurogenesis [as reviewed in Poulose et al. (2017)]. On the contrary, voluntary running or enriched environment are associated with enhanced AHN and with improvement of learning and memory (Fabel et al., 2009; Zainuddin and Thuret, 2012; Poulose et al., 2017; Kempermann, 2019). At the molecular level, modulation of AHN is mediated trough several signaling factors, including neurotrophic factors, transcriptional programs, inflammatory cytokines, neurotransmitters and hormones (Shohayeb et al., 2018), that are triggered by environmental demands. Many neurotrophic factors stimulate the activation of tropomyosin-related kinase (Trk) receptors, in turn activating intracellular signaling cascades that regulate NSC proliferation and fate. The role of neurotrophins and, in particular, of brain-derived neurotrophic factor (BDNF) in adult neurogenesis has been the subject of numerous studies; thus, BDNF-TrkB signaling positively regulates AHN and its dysregulation is associated with psychiatric and neurodegenerative disorders (Reichardt, 2006; Shohayeb et al., 2018).
Along with all these factors, over the last years emerged studies linking nutrition to AHN and mental health. Current literature suggests that dietary modifications can influence learning and memory as well as cognition and mood; so nutritional changes may be an inexpensive and relevant adjuvant intervention to boost mental and brain function (Zainuddin and Thuret, 2012; Murphy et al., 2014). Since neurogenesis can potentially regulate brain cognition and neuronal plasticity, nutritional factors that enhance neurogenesis may be attractive therapeutic targets for improving cognitive function and regulating different neurodegenerative and neuropsychiatric disorders [reviewed in Lim et al. (2021)].
In this mini-review, we summarize the existing scientific literature on the influence of nutrition and diet on AHN (Figure 1), as a possible mechanism by which nutrition impacts on cognition and mental health. It is important to consider that, while studies in humans have demonstrated that certain nutrients and diets modulate cognition and behavior, researching AHN in human samples is elusive due to current methodological limitations (Moreno-Jiménez et al., 2021). Therefore, the evidence linking nutrition and AHN that composes this review comes mainly from preclinical studies performed in rats and mice.
Figure 1. Impact of nutrition on adult hippocampal neurogenesis.
2. Nutrition as a regulatory factor in AHN
2.1. High-calorie diets and bioactive compounds
Learning and memory, closely related to AHN, can be influenced by diet during development and into adulthood; there is an inverse correlation between the quality of the diet and the disorders associated with these hippocampal abilities (Zainuddin and Thuret, 2012; Murphy et al., 2014). In this context, high-calorie diets (HCD), characterized in rodents by high levels of saturated fats (40–60% fat) and/or refined sugars for at least 4 weeks, strongly impairs in a sex specific manner AHN decreasing proliferating cells, differentiated neuroblasts/immature neurons and mature neurons; and has been associated with disfunctions in hippocampal-dependent memory and neuroinflammation, (Park et al., 2010; van der Borght et al., 2011; Hsu et al., 2015; Pérez-Garciá et al., 2016; Robison et al., 2020; Kim et al., 2021; Paulo et al., 2021; Fierros-Campuzano et al., 2022). Most of these studies affirm that the downregulation of the neurotrophin BDNF and its signaling through cAMP response element-binding (CREB) and TrkB as the main mechanism involved in HCD-induced AHN injury (Molteni et al., 2002; Hwang et al., 2008; White et al., 2009; Kim et al., 2021; Paulo et al., 2021). Other authors highlight the increase of serum corticosterone, malondialdehyde (MDA) and tumor necrosis factor alpha (TNFα) as responsible for this decrease in AHN induced by HFD (Lindqvist et al., 2006; Park et al., 2010; van der Borght et al., 2011).
Diets enriched with bioactive compounds, such as omega-3 fatty acids, vitamins and polyphenols (presents on blueberries, olive oil, coffee, cocoa, tea and curcumin, among others) enhance AHN (Sarubbo et al., 2018; Rajaram et al., 2019; Dias et al., 2021). Omega-3 fatty acids (ω-3 FAs) -present in fish, vegetable oils, nuts, flaxseed and leafy vegetables- can potentiate AHN through at least two distinct mechanisms; i.e., affecting the membrane fluidity and improving the serotonin binding (a neurotransmitter that stimulates neurogenesis) or by regulating neurotrophins levels like BDNF (Wu et al., 2004; Beltz et al., 2007) since they are part of the structural neuronal membranes. Additionally, ω-3 FAs improve spatial learning abilities in mice, which is associated with enhanced neurogenesis (Petursdottir et al., 2008; He et al., 2009; Valente et al., 2009).
Folates—an important regulator of central nervous system (CNS) development present in dark green leafy vegetables, beans, peas and nuts- could plays a critical role in the maintenance of AHN by its DNA methylation and epigenetic functions (Kronenberg et al., 2008). Its deficiency diminishes the concentration of neurotransmitters in the hippocampus, affecting AHN (Kronenberg et al., 2008; Zhang et al., 2012). Another vitamin, cobalamin—found in meat, fish, poultry, eggs and dairy products- also plays an essential role in proper brain development and function, impairing its lack of AHN due to its action on DNA replication and methylation (Smith, 2016).
Polyphenols, the biggest group of phytochemicals found in plant-based foods, are known for their biological antioxidative, neuroprotective, and cognitive properties, considered as exogenous molecules able to modulate adult neurogenesis (Valente et al., 2009). Several studies suggest that polyphenols induce AHN by increasing synaptic plasticity and promoting long-term hippocampal potentiation (Xu et al., 2007; An et al., 2008; Valente et al., 2009; Wang et al., 2011) as well as enhance learning and memory (Van Praag et al., 2007; Duffy et al., 2008; Rendeiro et al., 2012). Flavonoids-enriched diets, a class of polyphenol present in plants and plant-based foods, demonstrated an increase in the number of newly generated cells expressing the immature neuron marker doublecortin and mature neuron markers (Valente et al., 2009; Lee et al., 2010; Dias et al., 2012) and in the expression of two essential factors closely related to hippocampal neurogenesis: BDNF and the phosphorylated cyclic AMP-response element DNA-binding protein (pCREB) (An et al., 2008; Zainuddin and Thuret, 2012; Tan et al., 2017).
All the aforementioned emphasizes the importance of informing the population about the possible implications of HCD on cognitive effects, promoting the consumption of diets rich in bioactive compounds. In addition, it would be convenient to encourage the study of new natural compounds that may increase the AHN in humans, thus being able to improve memory and learning in people with cognitive deficits.
There are few studies focused on describing sex differences in relation to the influence of diet on AHN; however, there seems to be a strong sexual dimorphism. Since the differences between male and female physiologies are greatly influenced by hormonal differences and these in turn influence adult neurogenesis, studies are needed that relate sex hormone levels to nutrition and their influence on AHN.
2.2. Role of the microbiota in the impact of diet on AHN
Recently, gut microbiota has been revealed as a key factor to regulate both AHN and signaling molecules relevant to neuroplasticity that are altered by diet. There is a close bidirectional communication between the brain and the gut through the brain-gut-microbiota axis, formed by the central nervous system, the hypothalamus-pituitary-adrenal axis, the endocrine-immune system, the autonomic nervous system, and the gut microbiota (Carabotti et al., 2015; Cryan, 2018). Due to this two-way communication, signaling from the gut can alter brain function and vice versa. In this sense, a contribution of the intestinal microbiota to neurogenesis has been demonstrated in recent years. Probiotic administration can ameliorate hippocampal neurogenesis decline (Corpuz et al., 2018). Diet supplementation with Lactobacillus strains in an animal mouse model of accelerated aging improves cognitive performance in some behavioral test. Moreover, this supplementation in old female mice showed augmented BDNF, CREB and p-CREB in the hippocampus (Corpuz et al., 2018). Conversely, antibiotic administration decreased hippocampal neurogenesis and induced changes in the molecular signaling related to this process. For example, animals exposed to antimicrobials show a general inflammatory state (Guida et al., 2018), reduced hippocampal BDNF, increased TrkB receptor expression, depressive-like behavior in male mice, and impaired novel object recognition (hippocampus-dependent memory) (Fröhlich et al., 2016; Guida et al., 2018). Nevertheless, prebiotics and probiotics administration reversed the negative influence of antibiotics in neurogenesis in female and male mice (Möhle et al., 2016; Guida et al., 2018).
Several factors such as antibiotics, stress and diet can alter the gut microbiota composition, changing AHN (Cryan, 2018; Ribeiro et al., 2020; Guzzetta et al., 2022). Regarding diet, one study reported that mice on a HFD evidenced significant changes in the gut microbiota composition, decreasing principally bacteria of phylum Bacterioidetes, which are correlated with lower neuroinflammation and higher BDNF levels and memory performance (Jørgensen et al., 2014). Other authors showed that a high-fat diet (choline-deficient diet) induced gut dysbiosis, increasing the production of short-chain fatty acids (propionate and butyrate) by gut microbiota. This change evocate neuroinflammation, oxidative stress, synaptic loss, cell death in different brain regions, and premature increased neurogenesis (Ribeiro et al., 2020). Moreover, an obesogenic diet (high fat and sucrose) showed altered hippocampus-dependent learning measured by the Morris water maze test and alteration in the gut microbial community in male mice (Sun et al., 2022). This obesogenic diet also increased the expression of proinflammatory cytokines that evocate neuroinflammation and altered AHN. However, the polysaccharides administration with prebiotic function could reverse the effect of this obesogenic diet, confirming that the modulation of gut microbiota is a therapeutic target for some neurodevelopmental disorders (Sun et al., 2022).
Altogether, these recent results demonstrate that microbial signaling can control neurogenesis and synaptic plasticity. Moreover, regulating the gut microbiota could be a therapeutic target for many disorders that evocate changes in AHN, since the modulation of the microbiome will regulate AHN. It is necessary to explore in depth the effects of the administration of prebiotics, probiotics and symbiotics on pathological conditions, in different clinical and preclinical studies. This will corroborate the positive effect of these food products, and the potential role of AHN as a mediator of these effects. Specially, these treatments may be relevant when there is the coexistence of other pathology or environmental factor that increases the vulnerability to a psychiatric disorder o neurodegenerative disease.
2.3. Caloric restriction and intermittent fasting
Different preclinical models reported increased AHN in intermittent fasting (IF) or caloric restriction (CR). Caloric restriction models generally refer to a 30–40% decrease in daily caloric intake whereas animal IF models are defined as ad libitum feeding/no access 8 h/16 h or 12 h/12 h paradigms without caloric restriction.
There is a strong consensus in that IF and CR promote AHN; for example by increasing the number of immature neuroblasts (Dias et al., 2021), increasing the survival of neuronal precursor cells and their differentiation into mature neurons (Lee et al., 2002; Levenson and Rich, 2007; Kaptan et al., 2015; Baik et al., 2020); boost the number of shuttle shaped cells in the subgranular zone, the cell density in CA3 and the number of neurons and glia (Bondolfi et al., 2004; Liu et al., 2017; Mana et al., 2017; Cao et al., 2022; Xu et al., 2022). Only one study evidenced a decreased number of new hippocampal neurons in response to IF (Setel et al., 2022).
Several authors suggest different mechanisms underlying IF- and CR-induced AHN. Both paradigms have been related to an overall increment of the expression of neurotrophins (Elesawy et al., 2021), such as neurotrophin-3 (Park et al., 2008, 2013; Pani, 2015), ciliary neurotrophic factor (Park et al., 2008) and BDNF (Park et al., 2008; Treccani et al., 2014; van Praag et al., 2014; Kaptan et al., 2015; Kim et al., 2015; Morgan et al., 2017; Li et al., 2020; Brocchi et al., 2022; Setel et al., 2022) especially in newly generated neurons of the dentate gyrus (Lee et al., 2002; Elesawy et al., 2021). Caloric restricted animals displayed increased expression of genes of neuronal protection and differentiation, such as NeuroD1 (Brandhorst et al., 2015; Li et al., 2020), Notch (Baik et al., 2020), Klotho (Dias et al., 2021), Egr1 (Hornsby et al., 2016).
Dietary restriction was also associated with epigenetic changes. Animals exposed to CR displayed attenuation of age-related CG/CH methylation and prevention of age-related hypermethylation (Hadad et al., 2018) while IF stimulated the inhibition of histone deacetylase (van Praag et al., 2014) and simultaneously the deacetylation of genes delaying processes of cellular aging (Landry and Huang, 2021). Additionally, CR was associated with dampened expression of versican; an age-related protein with an essential role in neuronal development, maturation and survival (Setel et al., 2022). Animals who followed a restricted diet presented an increase of microRNA MMV-MIR-713: CR increases gene ontology of predicted microRNA targets of generation of neurons, neuron differentiation, and development (Cicekdal et al., 2022). CR also raised the expression of the gene PARP, which is associated with DNA repair and chromatin remodeling (Setel et al., 2022).
Several studies highlighted that IF and CR dependent neurogenesis is linked with increased expression of hippocampal NPY (Singh et al., 2015; Cao et al., 2022; Xu et al., 2022) and depends on increased quantities of hippocampal acyl-ghrelin (Kim et al., 2015; Hornsby et al., 2016) and ghrelin receptor (Hornsby et al., 2016). Notably, IF and CR also induced a CREB-dependent increase in SIRT1 and SIRT3 (Pani, 2015; Liu et al., 2019; Baik et al., 2020; Landry and Huang, 2021). Little evidence also showed a role for GSK3β (Li et al., 2020).
CR activates gene Foxo3, which improves adult neurogenesis through the reduction of neuroinflammation (Pani, 2015; Kim et al., 2020). In this context, animals displayed a decrease of proinflammatory hormones and cytokines (van Praag et al., 2014), reduced activation of glia (Liu et al., 2017; Li et al., 2020) and increased IFN-γ (promoting neural differentiation and neurite outgrowth in neural adult stem cells) (Park and Lee, 2011).
Finally, IF and CR reduced hippocampal oxidative stress and total protein oxidation content by increasing catalase reactivity and superoxide dismutase activity (Singh et al., 2015; Ahn et al., 2019) along with the expression of heat shock protein 70 and glucose-related protein 78 (involved in oxidative stress protection) (Landry and Huang, 2021).
To sum up, current literature demonstrates that both CR and IF can promote AHN. Of course, this finding has pivotal importance because of its high translational value in clinical practice: it could be an intervention of simple implementation in clinical protocols and has little to none adverse effects. However, further studies aimed to discover the exact mechanisms by which CR and IF promote AHN and what mediators/pathways are directly involved are needed. Moreover, most of the studies were done in healthy adult male subjects: more research is needed to underline the role of CR and IF in AHN in models of neurodegenerative pathologies (i.e., Alzheimer’s disease), in females (to evaluate the effect of gender) and at different age points (childhood, adolescence, elderly) and in female individuals.
3. Effect of maternal diet on offspring AHN
The perinatal environment, from pre-conception to lactation, is especially vulnerable to adverse conditions such as malnutrition or overnutrition, being able to permanently alter brain structure and function in the offspring. Thus, nutritional programming is partly responsible for cognition-related diseases in the offspring, even though clinical signs may only first arise in adulthood (Murray et al., 1991; Bolton and Bilbo, 2014; Rivera et al., 2020).
Adult hippocampal neurogenesis is sensitive to diet-related damage from direct consumption as we mentioned above (section 2.1) or from maternal exposure (Niculescu and Lupu, 2009; Mendes-da-Silva et al., 2014; Poulose et al., 2017). Maternal overfeeding during pregnancy and/or lactation greatly impacts adult neurogenesis in offspring (Niculescu and Lupu, 2009; Tozuka et al., 2009; Lépinay et al., 2015; Xavier et al., 2021). In this sense, consumption of a HFD during pregnancy leads to long-term effects in the central nervous system of the offspring, affecting neurogenesis-related pathways (Mash1 and BDNF) which correlated with the development of anhedonic-like behavior in the adulthood (Curi et al., 2021). Furthermore, perinatal exposure to HFD sensitizes the offspring to the adverse effects of postnatal high-fat intake on hippocampal function. This sensitization decreases AHN and reduces the expression of genes involved in hippocampal plasticity (Lépinay et al., 2015). Interestingly, it has been shown that the metabolic stress caused by the maternal consumption of HFD has a persistent influence, exerting multigenerational effects (up to the second and third generations) in the adult neurogenesis of their descendants; through an epigenetic disorder of pro-neurogenic genes in neural stem/progenitor cells (NSPC) (Natale et al., 2022).
Maternal consumption of a high-fructose diet during pregnancy and lactation decreased BDNF and suppressed hippocampal expression of Ki67 and DCX. These markers are related to NSPC division and neuronal differentiation; impairing hippocampal learning and memory in adult female offspring (Wu et al., 2016; Liu et al., 2020). These findings add to evidence suggesting that increased nuclear histone deacetylase 4 (HDAC4) activity induced by high-fructose maternal diets suppresses hippocampal neurogenesis in adult offspring.
Interestingly, few studies describe the impact of perinatal caloric restriction on offspring neurogenesis. Cell proliferation in the DG was significantly reduced in the offspring of mothers with 50% caloric restriction during pregnancy and/or lactation (Matos et al., 2011). Another study establishes an indirect relationship, demonstrating that the total and specific expression of the Igf2 allele (which regulates development, memory, and AHN) of the hippocampus is affected by maternal and grandmaternal moderate caloric restriction in a sex-specific manner (Harper et al., 2014).
In relation to this, prenatal protein restriction (8% protein diet during gestation and lactation) also reduces neuronal proliferation and BDNF expression in adult offspring, and is also associated with problems with memory encoding and consolidation (Pérez-Garciá et al., 2016).
It is well known that there are beneficial bioactive compounds during pregnancy and lactation for both the mother and the developing fetus; thus, many nutrients such as iron, zinc, selenium, iodine, folic acid, vitamin A, vitamin B6, vitamin B12 and choline are essential for neurodevelopment. Interestingly, some studies indicate that some of these compounds also improve the neurogenesis of offspring in adulthood; for example, prenatal iron deficiency results in long-term memory deficits (Lucassen et al., 2013); postnatal zinc supplementation improves cognitive impairment induced by zinc deficiency in early life, associated with abnormal expression of genes involved in DNA methylation and neurogenesis (Jiang et al., 2022).
Thus, maternal choline supplementation has been shown to improve cognitive function by increasing AHN in the offspring in both normal animals and animal models of neuropathologies such as Down syndrome and Alzheimer’s disease (Glenn et al., 2007; Cheng et al., 2008; Wong-Goodrich et al., 2008; Moon et al., 2010; Velazquez et al., 2013). Maternal supplementation with nicotinamide riboside (RN) during lactation also increase AHN in the offspring in rodents, which may be responsible for the neurobehavioral improvement, through enhanced nicotinamide adenine dinucleotide (NAD+) metabolism (Ear et al., 2019; Yang and Wan, 2019).
Maternal folic acid supplementation also promotes hippocampal neurogenesis and improves learning and memory in offspring, implicating mechanisms associated with DNA methylation in glucocorticoid receptor promoters and activation of BDNF/AKT/ERK1/2 signaling (Yang et al., 2019).
Preclinical studies have improved the understanding of the underlying mechanisms linking maternal intake and offspring neurodevelopment. In this sense, and in relation to what was previously described in section 2.2, the microbiota-gut-brain axis acts as a fundamental regulator of neurodevelopment (Dinan and Cryan, 2017; Ratsika et al., 2021). Maternal diet affects the composition of the maternal and neonatal gut microbiome in rodents, associated with abnormalities in brain function and behavior of the offspring (Paul et al., 2016; Vuong et al., 2020). Intake of a probiotic supplement during pregnancy and lactation has a long-lasting influence on behavior and neuroplasticity, mitigating anxiety-like behavior associated with maternal obesity (prolonged high-fat diet) in adult offspring. These improvements are associated with an increase in the expression of BDNF and other genes related to plasticity in adulthood of the offspring (Radford-Smith et al., 2022).
The findings summarized here confirm the importance of nutrition in neuronal plasticity from the perinatal stage. The mental health of an individual depends not only on himself but also in part on his progeny. However, this knowledge is not yet entrenched in society as there is still no great evidence at the clinical level. Thus, more studies in humans where maternal, and probably paternal, nutritional states are correlated with long-term cognitive alterations in offspring are necessaries. Those data has been difficult to collect up to now due to the absence of computerized records of the perinatal stage. Another limitation at the clinical level compared to animal models is the difficulty of studying AHN directly. For this reason, the gut-brain connection through the study of the microbiota opens an interesting topic of study, not only in adult individuals but also from their gestation. The analysis of the microbiota in relation to nutrition and its correlation with genes related to neuronal plasticity and plasmatic neurogenic markers will provide great information on the mechanisms involved in neuroplasticity and will open both preventive and therapeutic action pathways against cognitive disorders and neurodegenerative diseases.
4. Conclusion
The current literature provides solid evidence about the fundamental role of dietary factors in hippocampal plasticity. Malnutrition from the fetal stage and/or throughout life contributes to the acceleration of age-related deterioration, positioning diet as an important factor in the risk, progression, and severity of the mental diseases. It can be concluded that an adequate dietary intake from the perinatal stage to adulthood, considering quantity, frequency and content of food or bioactive compounds, should be considered and promoted as a public health initiative for the prevention and improvement of neuropsychiatric disorders.
Modulation of AHN by diet could emerge as a possible mechanism by which nutrition impacts on mental health. Despite the knowledge of the large implication of factors such as BDNF, and the promising role of factors such as gut microbiota, further investigation of the mechanisms by which prenatal and early postnatal life nutritional factors influence AHN -and consequently cognitive function- would contribute to understanding this relationship and would have important implications for dietary modification of brain’s response to injury and disease. Nevertheless, research on AHN in humans is still at an early stage and more translational research is needed to confirm a functional role of AHN in the human brain as well as its modulation by diet.
Most of the studies reviewed here do not contemplate the possible differentiating effect of diet on the AHN of male and female animals. In general, studies based on nutritional programming on offspring AHN include both male and female offspring, but even so, some of them do not focus on possible sexual dimorphism. However, studies on the nutrition-AHN relationship that include male and female animals show sex-specific dietary effects, with females generally being more susceptible.
Author contributions
EC-O, AC-Z, and PR designed the study. All authors performed the research, wrote the manuscript, have made a substantial, direct, and intellectual contribution to the work, and approved it for publication.
Funding
This study was funded by grant PID2020-114374RB-I00 funded by MCIN/AEI/10.13039/501100011033 (CR-P and EC-O); Junta de Andalucía-Consejería de Universidad, Investigación e Innovación - Proyecto P21_00777 (CR-P and EC-O); Ministerio de Sanidad, Delegación de Gobierno para el Plan Nacional sobre Drogas grant number 2020/048; Consejería de Universidad, Investigación e Innovación grant number PROYEXCEL_0029. P.R. (CP19/00068) holds a “Miguel Servet I” research contract from the National System of Health, ERDF-EU-ISCIII. MC holds a postdoctoral research contract from Consejeria de Salud – Junta de Andalucia (RH 0081-2021).
Acknowledgments
This is a short text to acknowledge the contributions of specific colleagues, institutions, or agencies that aided the efforts of the authors.
Conflict of interest
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Publisher’s note
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References
Ahn, J. H., Shin, B. N., Song, M., Kim, H., Park, J. H., Lee, T. K., et al. (2019). Intermittent fasting increases the expressions of SODs and catalase in granule and polymorphic cells and enhances neuroblast dendrite complexity and maturation in the adult gerbil dentate gyrus. Mol. Med. Rep. 19, 1721–1727. doi: 10.3892/mmr.2019.9822
An, L., Zhang, Y. Z., Yu, N. J., Liu, X. M., Zhao, N., Yuan, L., et al. (2008). The total flavonoids extracted from Xiaobuxin-Tang up-regulate the decreased hippocampal neurogenesis and neurotrophic molecules expression in chronically stressed rats. Prog. Neuro Psychopharmacol. Biol. Psychiatry 32, 1484–1490. doi: 10.1016/j.pnpbp.2008.05.005
Baik, S. H., Rajeev, V., Fann, D. Y. W., Jo, D. G., and Arumugam, T. V. (2020). Intermittent fasting increases adult hippocampal neurogenesis. Brain Behav. 10:e01444. doi: 10.1002/brb3.1444
Beltz, B. S., Tlusty, M. F., Benton, J. L., and Sandeman, D. C. (2007). Omega-3 fatty acids upregulate adult neurogenesis. Neurosci. Lett. 415, 154–158. doi: 10.1016/j.neulet.2007.01.010
Bolton, J. L., and Bilbo, S. D. (2014). Developmental programming of brain and behavior by perinatal diet: focus on inflammatory mechanisms. Dialogues Clin. Neurosci. 16, 307–320. doi: 10.31887/DCNS.2014.16.3/jbolton
Bondolfi, L., Ermini, F., Long, J. M., Ingram, D. K., and Jucker, M. (2004). Impact of age and caloric restriction on neurogenesis in the dentate gyrus of C57BL/6 mice. Neurobiol. Aging 25, 333–340. doi: 10.1016/S0197-4580(03)00083-6
Brandhorst, S., Choi, I. Y., Wei, M., Cheng, C. W., Sedrakyan, S., Navarrete, G., et al. (2015). a periodic diet that mimics fasting promotes multi-system regeneration, enhanced cognitive performance, and healthspan. Cell Metab. 22, 86–99. doi: 10.1016/j.cmet.2015.05.012
Brocchi, A., Rebelos, E., Dardano, A., Mantuano, M., and Daniele, G. (2022). Effects of intermittent fasting on brain metabolism. Nutrients 14:1275. doi: 10.3390/nu14061275
Cao, S., Li, M., Sun, Y., Wu, P., Yang, W., Dai, H., et al. (2022). Intermittent fasting enhances hippocampal NPY expression to promote neurogenesis after traumatic brain injury. Nutrition 97:111621. doi: 10.1016/j.nut.2022.111621
Carabotti, M., Scirocco, A., Maselli, M. A., and Severi, C. (2015). The gut-brain axis: interactions between enteric microbiota, central and enteric nervous systems. Ann. Gastroenterol. 28, 203–209.
Castilla-Ortega, E., Pedraza, C., Estivill-Torrús, G., and Santín, L. J. (2011). When is adult hippocampal neurogenesis necessary for learning? evidence from animal research. Rev. Neurosci. 22, 267–283. doi: 10.1515/rns.2011.027
Cheng, R. K., MacDonald, C. J., Williams, C. L., and Meck, W. H. (2008). Prenatal choline supplementation alters the timing, emotion, and memory performance (TEMP) of adult male and female rats as indexed by differential reinforcement of low-rate schedule behavior. Learn. Mem. 15, 153–162. doi: 10.1101/lm.729408
Cicekdal, M. B., Kuskucu, A., Bayrak, O. F., Yilmaz, B., Demirel, P. B., Cleary, M. P., et al. (2022). Long-term chronic caloric restriction alters miRNA profiles in the brain of ageing mice. Br. J. Nutr. 127, 641–652. doi: 10.1017/S0007114521001239
Clelland, C. D., Choi, M., Romberg, C., Clemenson, G. D., Fragniere, A., Tyers, P., et al. (2009). A functional role for adult hippocampal neurogenesis in spatial pattern separation. Science 325, 210–213. doi: 10.1126/science.1173215
Corpuz, H. M., Ichikawa, S., Arimura, M., Mihara, T., Kumagai, T., Mitani, T., et al. (2018). Long-term diet supplementation with lactobacillus paracasei K71 prevents age-related cognitive decline in senescence-accelerated mouse prone 8. Nutrients 10:762. doi: 10.3390/nu10060762
Cryan, J. (2018). The gut microbiome: a key regulator of neurodevelopment and behaviour. Schizophr. Bull. 44, S59–S60. doi: 10.1093/schbul/sby014.152
Curi, H. T., Dias, C. T., da Luz Camargo, M. L. M., and dos Santos Gomez, P. (2021). Maternal high-fat diet increases anhedonic behavior and modulates hippocampal Mash1 and BDNF expression in adult offspring. Neurosci. Lett. 764:136239. doi: 10.1016/j.neulet.2021.136239
Dias, G. P., Cavegn, N., Nix, A., Do Nascimento Bevilaqua, M. C., and Stangl, D. (2012). The role of dietary polyphenols on adult hippocampal neurogenesis: molecular mechanisms and behavioural effects on depression and anxiety. Oxid. Med. Cell. Longev. 2012:541971. doi: 10.1155/2012/541971
Dias, G. P., Murphy, T., Stangl, D., Ahmet, S., Morisse, B., Nix, A., et al. (2021). Intermittent fasting enhances long-term memory consolidation, adult hippocampal neurogenesis, and expression of longevity gene Klotho. Mol. Psychiatry 26, 6365–6379. doi: 10.1038/s41380-021-01102-4
Dinan, T. G., and Cryan, J. F. (2017). Gut instincts: microbiota as a key regulator of brain development, ageing and neurodegeneration. J. Physiol. 595, 489–503. doi: 10.1113/JP273106
Duffy, K. B., Spangler, E. L., Devan, B. D., Guo, Z., Bowker, J. L., Janas, A. M., et al. (2008). A blueberry-enriched diet provides cellular protection against oxidative stress and reduces a kainate-induced learning impairment in rats. Neurobiol. Aging 29, 1680–1689. doi: 10.1016/j.neurobiolaging.2007.04.002
Ear, P. H., Chadda, A., Gumusoglu, S. B., Schmidt, M. S., Vogeler, S., Malicoat, J., et al. (2019). Maternal nicotinamide riboside enhances postpartum weight loss, juvenile offspring development, and neurogenesis of adult offspring. Cell Rep. 26, 969–983.e4. doi: 10.1016/j.celrep.2019.01.007
Elesawy, B. H., Raafat, B. M., Al Muqbali, A., Abbas, A. M., and Sakr, H. F. (2021). The impact of intermittent fasting on brain-derived neurotrophic factor, neurotrophin 3, and rat behavior in a rat model of type 2 diabetes mellitus. Brain Sci. 11:242. doi: 10.3390/brainsci11020242
Eriksson, P. S., Perfilieva, E., Björk-Eriksson, T., Alborn, A. M., Nordborg, C., Peterson, D. A., et al. (1998). Neurogenesis in the adult human hippocampus. Nat. Med. 4, 1313–1317. doi: 10.1038/3305
Fabel, K., Wolf, S. A., Ehninger, D., Babu, H., Leal-Galicia, P., and Kempermann, G. (2009). Additive effects of physical exercise and environmental enrichment on adult hippocampal neurogenesis in mice. Front. Neurosci. 3:50. doi: 10.3389/neuro.22.002.2009
Fierros-Campuzano, J., Ballesteros-Zebadúa, P., Manjarrez-Marmolejo, J., Aguilera, P., Méndez-Diaz, M., Prospero-García, O., et al. (2022). Irreversible hippocampal changes induced by high fructose diet in rats. Nutr. Neurosci. 25, 1325–1337. doi: 10.1080/1028415X.2020.1853418
Fröhlich, E. E., Farzi, A., Mayerhofer, R., Reichmann, F., Jačan, A., Wagner, B., et al. (2016). Cognitive impairment by antibiotic-induced gut dysbiosis: analysis of gut microbiota-brain communication. Brain. Behav. Immun. 56, 140–155. doi: 10.1016/j.bbi.2016.02.020
Glenn, M. J., Gibson, E. M., Kirby, E. D., Mellott, T. J., Blusztajn, J. K., and Williams, C. L. (2007). Prenatal choline availability modulates hippocampal neurogenesis and neurogenic responses to enriching experiences in adult female rats. Eur. J. Neurosci. 25, 2473–2482. doi: 10.1111/j.1460-9568.2007.05505.x
Gould, E., and Gross, C. G. (2002). Neurogenesis in adult mammals: some progress and problems. J. Neurosci. 22, 619–623. doi: 10.1523/JNEUROSCI.22-03-00619.2002
Guida, F., Turco, F., Iannotta, M., De Gregorio, D., Palumbo, I., Sarnelli, G., et al. (2018). Antibiotic-induced microbiota perturbation causes gut endocannabinoidome changes, hippocampal neuroglial reorganization and depression in mice. Brain. Behav. Immun. 67, 230–245. doi: 10.1016/j.bbi.2017.09.001
Guzzetta, K. E., Cryan, J. F., and O’Leary, O. F. (2022). Microbiota-gut-brain axis regulation of adult hippocampal neurogenesis. Brain Plast. 8, 97–119.
Hadad, N., Unnikrishnan, A., Jackson, J. A., Masser, D. R., Otalora, L., Stanford, D. R., et al. (2018). Caloric restriction mitigates age-associated hippocampal differential CG and non-CG methylation. Neurobiol. Aging 67, 53–66. doi: 10.1016/j.neurobiolaging.2018.03.009
Harper, K. M., Tunc-Ozcan, E., Graf, E. N., Herzing, L. B. K., and Redei, E. E. (2014). Intergenerational and parent of origin effects of maternal calorie restriction on Igf2 expression in the adult rat hippocampus. Psychoneuroendocrinology 45, 187–191. doi: 10.1016/j.psyneuen.2014.04.002
He, C., Qu, X., Cui, L., Wang, J., and Kang, J. X. (2009). Improved spatial learning performance of fat-1 mice is associated with enhanced neurogenesis and neuritogenesis by docosahexaenoic acid. Proc. Natl. Acad. Sci. U. S. A. 106, 11370–11375. doi: 10.1073/pnas.0904835106
Hornsby, A. K. E., Redhead, Y. T., Rees, D. J., Ratcliff, M. S. G., Reichenbach, A., Wells, T., et al. (2016). Short-term calorie restriction enhances adult hippocampal neurogenesis and remote fear memory in a Ghsr-dependent manner. Psychoneuroendocrinology 63, 198–207. doi: 10.1016/j.psyneuen.2015.09.023
Hsu, T. M., Konanur, V. R., Taing, L., Usui, R., Kayser, B. D., Goran, M. I., et al. (2015). Effects of sucrose and high fructose corn syrup consumption on spatial memory function and hippocampal neuroinflammation in adolescent rats. Hippocampus 25, 227–239. doi: 10.1002/hipo.22368
Hwang, I. K., Kim, I. Y., Kim, D. W., Yoo, K. Y., Kim, Y. N., Yi, S. S., et al. (2008). Strain-specific differences in cell proliferation and differentiation in the dentate gyrus of C57BL/6N and C3H/HeN mice fed a high fat diet. Brain Res. 1241, 1–6. doi: 10.1016/j.brainres.2008.08.024
Jiang, Y. G., Wang, Y. H., Zhang, H., Wang, Z. Y., and Liu, Y. Q. (2022). Effects of early-life zinc deficiency on learning and memory in offspring and the changes in DNA methylation patterns. Nutr. Neurosci. 25, 1001–1010. doi: 10.1080/1028415X.2020.1831259
Jørgensen, B. P., Hansen, J. T., Krych, L., Larsen, C., Klein, A. B., Nielsen, D. S., et al. (2014). A possible link between food and mood: dietary impact on gut microbiota and behavior in BALB/c mice. PLoS One 9:e103398. doi: 10.1371/journal.pone.0103398
Kaptan, Z., Akgün-Dar, K., Kapucu, A., Dedeakayoʇullari, H., Batu, S., and Üzüm, G. (2015). Long term consequences on spatial learning-memory of low-calorie diet during adolescence in female rats; Hippocampal and prefrontal cortex BDNF level, expression of NeuN and cell proliferation in dentate gyrus. Brain Res. 1618, 194–204. doi: 10.1016/j.brainres.2015.05.041
Kee, N., Teixeira, C. M., Wang, A. H., and Frankland, P. W. (2007). Preferential incorporation of adult-generated granule cells into spatial memory networks in the dentate gyrus. Nat. Neurosci. 10, 355–362. doi: 10.1038/nn1847
Kempermann, G. (2019). Environmental enrichment, new neurons and the neurobiology of individuality. Nat. Rev. Neurosci. 20, 235–245.
Kim, C., Pinto, A. M., Bordoli, C., Buckner, L. P., Kaplan, P. C., Del Arenal, I. M., et al. (2020). Energy restriction enhances adult hippocampal neurogenesis-associated memory after four weeks in an adult human population with central obesity; a randomized controlled trial. Nutrients 12:638. doi: 10.3390/nu12030638
Kim, W., Kwon, H. J., Jung, H. Y., Lim, S. S., Kang, B. G., Jo, Y. B., et al. (2021). Extracts from the leaves of Cissus verticillata ameliorate high-fat diet-induced memory deficits in mice. Plants 10:1814. doi: 10.3390/plants10091814
Kim, Y., Kim, S., Kim, C., Sato, T., Kojima, M., and Park, S. (2015). Ghrelin is required for dietary restriction-induced enhancement of hippocampal neurogenesis: lessons from ghrelin knockout mice. Endocr. J. 62, 269–275. doi: 10.1507/endocrj.EJ14-0436
Koehl, M., and Abrous, D. N. (2011). A new chapter in the field of memory: adult hippocampal neurogenesis. Eur. J. Neurosci. 33, 1101–1114.
Kronenberg, G., Harms, C., Sobol, R. W., Cardozo-Pelaez, F., Linhart, H., Winter, B., et al. (2008). Folate deficiency induces neurodegeneration and brain dysfunction in mice lacking uracil DNA glycosylase. J. Neurosci. 28, 7219–7230.
Landry, T., and Huang, H. (2021). Mini review: the relationship between energy status and adult hippocampal neurogenesis. Neurosci. Lett. 765:136261. doi: 10.1016/j.neulet.2021.136261
Lee, J., Duan, W., and Mattson, M. P. (2002). Evidence that brain-derived neurotrophic factor is required for basal neurogenesis and mediates, in part, the enhancement of neurogenesis by dietary restriction in the hippocampus of adult mice. J. Neurochem. 82, 1367–1375. doi: 10.1046/j.1471-4159.2002.01085.x
Lee, S., Kim, D. H., Lee, D. H., Jeon, S. J., Lee, C. H., Son, K. H., et al. (2010). Oroxylin a, a flavonoid, stimulates adult neurogenesis in the hippocampal dentate gyrus region of mice. Neurochem. Res. 35, 1725–1732. doi: 10.1007/s11064-010-0235-y
Lépinay, A. L., Larrieu, T., Joffre, C., Acar, N., Gárate, I., Castanon, N., et al. (2015). Perinatal high-fat diet increases hippocampal vulnerability to the adverse effects of subsequent high-fat feeding. Psychoneuroendocrinology 53, 82–93. doi: 10.1016/j.psyneuen.2014.12.008
Leuner, B., Gould, E., and Shors, T. J. (2006). Is there a link between adult neurogenesis and learning? Hippocampus 16, 578–584. doi: 10.1002/hipo.20153
Levenson, C. W., and Rich, N. J. (2007). Eat less, live longer? new insights into the role of caloric restriction in the brain. Nutr. Rev. 65, 412–415. doi: 10.1111/j.1753-4887.2007.tb00319.x
Li, W., Wu, M., Zhang, Y., Wei, X., Zang, J., Liu, Y., et al. (2020). Intermittent fasting promotes adult hippocampal neuronal differentiation by activating GSK-3β in 3xTg-AD mice. J. Neurochem. 155, 697–713. doi: 10.1111/jnc.15105
Lim, J., Kim, H. I., Bang, Y., and Choi, H. J. (2021). Peroxisome proliferator-activated receptor gamma: a novel therapeutic target for cognitive impairment and mood disorders that functions via the regulation of adult neurogenesis. Arch. Pharm. Res. 44, 553–563. doi: 10.1007/s12272-021-01333-7
Lindqvist, A., Mohapel, P., Bouter, B., Frielingsdorf, H., Pizzo, D., Brundin, P., et al. (2006). High-fat diet impairs hippocampal neurogenesis in male rats. Eur. J. Neurol. 13, 1385–1388.
Liu, W. C., Wu, C. W., Hung, P. L., Chan, J. Y. H., Tain, Y. L., Fu, M. H., et al. (2020). Environmental stimulation counteracts the suppressive effects of maternal high-fructose diet on cell proliferation and neuronal differentiation in the dentate gyrus of adult female offspring via histone deacetylase 4. Int. J. Environ. Res. Public Health 17:3919. doi: 10.3390/ijerph17113919
Liu, Y., Cheng, A., Li, Y. J., Yang, Y., Kishimoto, Y., Zhang, S., et al. (2019). SIRT3 mediates hippocampal synaptic adaptations to intermittent fasting and ameliorates deficits in APP mutant mice. Nat. Commun. 10:1886. doi: 10.1038/s41467-019-09897-1
Liu, Y., Wang, R., Zhao, Z., Dong, W., Zhang, X., Chen, X., et al. (2017). Short-term caloric restriction exerts neuroprotective effects following mild traumatic brain injury by promoting autophagy and inhibiting astrocyte activation. Behav. Brain Res. 331, 135–142. doi: 10.1016/j.bbr.2017.04.024
Lucassen, P. J., Naninck, E. F. G., van Goudoever, J. B., Fitzsimons, C., Joels, M., and Korosi, A. (2013). Perinatal programming of adult hippocampal structure and function; Emerging roles of stress, nutrition and epigenetics. Trends Neurosci. 36, 621–631. doi: 10.1016/j.tins.2013.08.002
Mana, M. D., Kuo, E. Y. S., and Yilmaz, ÖH. (2017). Dietary regulation of adult stem cells. Curr. Stem Cell Rep. 3, 1–8.
Matos, R. J. B., Orozco-Solís, R., Lopes de Souza, S., Manhães-de-Castro, R., and Bolaños-Jiménez, F. (2011). Nutrient restriction during early life reduces cell proliferation in the hippocampus at adulthood but does not impair the neuronal differentiation process of the new generated cells. Neuroscience 196, 16–24. doi: 10.1016/j.neuroscience.2011.08.071
Mendes-da-Silva, C., Giriko, C. Á, Mennitti, L. V., Hosoume, L. F., Souto, T. D. S., and da Silva, A. V. (2014). Maternal high-fat diet during pregnancy or lactation changes the somatic and neurological development of the offspring. Arq. Neuropsiquiatr. 72, 136–144.
Möhle, L., Mattei, D., Heimesaat, M. M., Bereswill, S., Fischer, A., Alutis, M., et al. (2016). Ly6Chi monocytes provide a link between antibiotic-induced changes in gut microbiota and adult hippocampal neurogenesis. Cell Rep. 15, 1945–1956. doi: 10.1016/j.celrep.2016.04.074
Molteni, R., Barnard, R. J., Ying, Z., Roberts, C. K., and Gómez-Pinilla, F. (2002). A high-fat, refined sugar diet reduces hippocampal brain-derived neurotrophic factor, neuronal plasticity, and learning. Neuroscience 112, 803–814. doi: 10.1016/s0306-4522(02)00123-9
Moon, J., Chen, M., Gandhy, S. U., Strawderman, M., Levitsky, D. A., Maclean, K. N., et al. (2010). Perinatal choline supplementation improves cognitive functioning and emotion regulation in the Ts65Dn mouse model of down syndrome. Behav. Neurosci. 124, 346–361. doi: 10.1037/a0019590
Moreno-Jiménez, E. P., Terreros-Roncal, J., Flor-García, M., Rábano, A., and Llorens-Martín, M. (2021). Evidences for adult hippocampal neurogenesis in humans. J. Neurosci. 41, 2541–2553.
Morgan, A. H., Andrews, Z. B., and Davies, J. S. (2017). Less is more: caloric regulation of neurogenesis and adult brain function. J. Neuroendocrinol. 29:e12512. doi: 10.1111/jne.12512
Murphy, T., Dias, G. P., and Thuret, S. (2014). Effects of diet on brain plasticity in animal and human studies: mind the gap. Neural Plast. 2014:563160. doi: 10.1155/2014/563160
Murray, R. M., Jones, P., and O’Callaghan, E. (1991). Fetal brain development and later schizophrenia. Ciba Found. Symp. 156, 155–163.
Natale, F., Spinelli, M., Barbati, S. A., Leone, L., Fusco, S., and Grassi, C. (2022). High fat diet multigenerationally affects hippocampal neural stem cell proliferation via epigenetic mechanisms. Cells 11:2661. doi: 10.3390/cells11172661
Niculescu, M. D., and Lupu, D. S. (2009). High fat diet-induced maternal obesity alters fetal hippocampal development. Int. J. Dev. Neurosci. 27, 627–633.
Pani, G. (2015). Neuroprotective effects of dietary restriction: evidence and mechanisms. Semin. Cell Dev. Biol. 40, 106–114.
Park, H. R., and Lee, J. (2011). Neurogenic contributions made by dietary regulation to hippocampal neurogenesis. Ann. N. Y. Acad. Sci. 1229, 23–28.
Park, H. R., Park, M., Choi, J., Park, K. Y., Chung, H. Y., and Lee, J. (2010). A high-fat diet impairs neurogenesis: involvement of lipid peroxidation and brain-derived neurotrophic factor. Neurosci. Lett. 482, 235–239. doi: 10.1016/j.neulet.2010.07.046
Park, H. R., Park, M., Kim, H. S., and Lee, J. (2008). Molecular mechanism of dietary restriction in neuroprevention and neurogenesis: involvement of neurotrophic factors. Toxicol. Res. 24, 245–251. doi: 10.5487/TR.2008.24.4.245
Park, J. H., Glass, Z., Sayed, K., Michurina, T. V., Lazutkin, A., Mineyeva, O., et al. (2013). Calorie restriction alleviates the age-related decrease in neural progenitor cell division in the aging brain. Eur. J. Neurosci. 37, 1987–1993. doi: 10.1111/ejn.12249
Paul, H. A., Bomhof, M. R., Vogel, H. J., and Reimer, R. A. (2016). Diet-induced changes in maternal gut microbiota and metabolomic profiles influence programming of offspring obesity risk in rats. Sci. Rep. 6:20683. doi: 10.1038/srep20683
Paulo, S. L., Miranda-Lourenço, C., Belo, R. F., Rodrigues, R. S., Fonseca-Gomes, J., Tanqueiro, S. R., et al. (2021). High caloric diet induces memory impairment and disrupts synaptic plasticity in aged rats. Curr. Issues Mol. Biol. 43, 2305–2319. doi: 10.3390/cimb43030162
Pérez-Garciá, G., Guzmán-Quevedo, O., Da Silva Aragaõ, R., and Bolanõs-Jiménez, F. (2016). Early malnutrition results in long-lasting impairments in pattern-separation for overlapping novel object and novel location memories and reduced hippocampal neurogenesis. Sci. Rep. 6:21275. doi: 10.1038/srep21275
Petursdottir, A. L., Farr, S. A., Morley, J. E., Banks, W. A., and Skuladottir, G. V. (2008). Effect of dietary n-3 polyunsaturated fatty acids on brain lipid fatty acid composition, learning ability, and memory of senescence-accelerated mouse. J. Gerontol. A Biol. Sci. Med. Sci. 63, 1153–1160. doi: 10.1093/gerona/63.11.1153
Poulose, S. M., Miller, M. G., Scott, T., and Shukitt-Hale, B. (2017). Nutritional factors affecting adult neurogenesis and cognitive function. Adv. Nutr. 8, 804–811.
Radford-Smith, D. E., Probert, F., Burnet, P. W. J., and Anthony, D. C. (2022). Modifying the maternal microbiota alters the gut–brain metabolome and prevents emotional dysfunction in the adult offspring of obese dams. Proc. Natl. Acad. Sci. U. S. A. 119:e2108581119. doi: 10.1073/pnas.2108581119
Rajaram, S., Jones, J., and Lee, G. J. (2019). Plant-based dietary patterns, plant foods, and age-related cognitive decline. Adv. Nutr. 10, S422–S436.
Ratsika, A., Codagnone, M. C., O’mahony, S., Stanton, C., and Cryan, J. F. (2021). Priming for life: early life nutrition and the microbiota-gut-brain axis. Nutrients 13:423.
Reichardt, L. F. (2006). Neurotrophin-regulated signalling pathways. Philos. Trans. R. Soc. B Biol. Sci. 361, 1545–1564.
Rendeiro, C., Vauzour, D., Kean, R. J., Butler, L. T., Rattray, M., Spencer, J. P. E., et al. (2012). Blueberry supplementation induces spatial memory improvements and region-specific regulation of hippocampal BDNF mRNA expression in young rats. Psychopharmacology 223, 319–330. doi: 10.1007/s00213-012-2719-8
Ribeiro, M. F., Santos, A. D. S. A., Afonso, M. B., Rodrigues, P. M., Sá Santos, S., Castro, R. E., et al. (2020). Diet-dependent gut microbiota impacts on adult neurogenesis through mitochondrial stress modulation. Brain Commun. 2:fcaa165. doi: 10.1093/braincomms/fcaa165
Rivera, P., Tovar, R., Ramírez-López, M. T., Navarro, J. A., Vargas, A., Suárez, J., et al. (2020). Sex-specific anxiety and prefrontal cortex glutamatergic dysregulation are long-term consequences of pre-and postnatal exposure to hypercaloric diet in a rat model. Nutrients 12:1829. doi: 10.3390/nu12061829
Robison, L. S., Albert, N. M., Camargo, L. A., Anderson, B. M., Salinero, A. E., Riccio, D. A., et al. (2020). High-fat diet-induced obesity causes sex-specific deficits in adult hippocampal neurogenesis in mice. eNeuro 7:ENEURO.0391–19.2019. doi: 10.1523/ENEURO.0391-19.2019
Sarubbo, F., Moranta, D., and Pani, G. (2018). Dietary polyphenols and neurogenesis: molecular interactions and implication for brain ageing and cognition. Neurosci. Biobehav. Rev. 90, 456–470. doi: 10.1016/j.neubiorev.2018.05.011
Schmidt-Hieber, C., Jones, P., and Bischofberger, J. (2004). Enhanced synaptic plasticity in newly generated granule cells of the adult hippocampus. Nature 429, 184–187.
Setel, D. D., Beker, M., Terzioglu-Usak, S., and Elibol, B. (2022). Astragalus membranaceus treatment combined with caloric restriction may enhance genesis factors and decrease apoptosis in the hippocampus of rats. Arch. Gerontol. Geriatr. 99:104584. doi: 10.1016/j.archger.2021.104584
Shohayeb, B., Diab, M., Ahmed, M., and Ng, D. C. H. (2018). Factors that influence adult neurogenesis as potential therapy. Transl. Neurodegener. 7:4.
Singh, R., Manchanda, S., Kaur, T., Kumar, S., Lakhanpal, D., Lakhman, S. S., et al. (2015). Middle age onset short-term intermittent fasting dietary restriction prevents brain function impairments in male Wistar rats. Biogerontology 16, 755–788. doi: 10.1007/s10522-015-9603-y
Smith, A. D. (2016). Hippocampus as a mediator of the role of Vitamin B-12 in memory. Am. J. Clin. Nutr. 103, 959–960. doi: 10.3945/ajcn.116.132266
Squire, L. R. (1992). “Memory and the hippocampus: a synthesis from findings with rats, monkeys, and humans”: correction. Psychol. Rev. 99, 195–231.
Sun, P., Wang, M., Li, Z., Wei, J., Liu, F., Zheng, W., et al. (2022). Eucommiae cortex polysaccharides mitigate obesogenic diet-induced cognitive and social dysfunction via modulation of gut microbiota and tryptophan metabolism. Theranostics 12, 3637–3655. doi: 10.7150/thno.72756
Tan, L., Yang, H., Pang, W., Li, H., Liu, W., Sun, S., et al. (2017). Investigation on the role of BDNF in the benefits of blueberry extracts for the improvement of learning and memory in Alzheimer’s disease mouse model. J. Alzheimer’s Dis. 56, 629–640. doi: 10.3233/JAD-151108
Tozuka, Y., Wada, E., and Wada, K. (2009). Diet-induced obesity in female mice leads to peroxidized lipid accumulations and impairment of hippocampal neurogenesis during the early life of their offspring. FASEB J. 23, 1920–1934. doi: 10.1096/fj.08-124784
Treccani, G., Musazzi, L., Perego, C., Milanese, M., Nava, N., Bonifacino, T., et al. (2014). Stress and corticosterone increase the readily releasable pool of glutamate vesicles in synaptic terminals of prefrontal and frontal cortex. Mol. Psychiatry. 19, 433–443.
Valente, T., Hidalgo, J., Bolea, I., Ramirez, B., Anglés, N., Reguant, J., et al. (2009). A diet enriched in polyphenols and polyunsaturated fatty acids, LMN diet, induces neurogenesis in the subventricular zone and hippocampus of adult mouse brain. J. Alzheimer’s Dis. 18, 849–865. doi: 10.3233/JAD-2009-1188
van der Borght, K., Köhnke, R., Göransson, N., Deierborg, T., Brundin, P., Erlanson-Albertsson, C., et al. (2011). Reduced neurogenesis in the rat hippocampus following high fructose consumption. Regul. Pept. 167, 26–30. doi: 10.1016/j.regpep.2010.11.002
Van Praag, H., Lucero, M. J., Yeo, G. W., Stecker, K., Heivand, N., Zhao, C., et al. (2007). Plant-derived flavanol (-)epicatechin enhances angiogenesis and retention of spatial memory in mice. J. Neurosci. 27, 5869–5878. doi: 10.1523/JNEUROSCI.0914-07.2007
van Praag, X., Fleshner, M., Schwartz, M. W., and Mattson, M. P. (2014). Exercise, energy intake, glucose homeostasis, and the brain. J. Neurosci. 34, 15139–15149.
Velazquez, R., Ash, J. A., Powers, B. E., Kelley, C. M., Strawderman, M., Luscher, Z. I., et al. (2013). Maternal choline supplementation improves spatial learning and adult hippocampal neurogenesis in the Ts65Dn mouse model of Down syndrome. Neurobiol. Dis. 58, 92–101.
Vuong, H. E., Pronovost, G. N., Williams, D. W., Coley, E. J. L., Siegler, E. L., Qiu, A., et al. (2020). The maternal microbiome modulates fetal neurodevelopment in mice. Nature 586, 281–286. doi: 10.1038/s41586-020-2745-3
Wang, S., Scott, B. W., and Wojtowicz, J. M. (2000). Heterogenous properties of dentate granule neurons in the adult rat. J. Neurobiol. 42, 248–257.
Wang, W., Wang, F., Yang, Y. J., Hu, Z. L., Long, L. H., Fu, H., et al. (2011). The flavonoid baicalein promotes NMDA receptor-dependent long-term potentiation and enhances memory. Br. J. Pharmacol. 162, 1364–1379. doi: 10.1111/j.1476-5381.2010.01143.x
White, C. L., Pistell, P. J., Purpera, M. N., Gupta, S., Fernandez-Kim, S. O., Hise, T. L., et al. (2009). Effects of high fat diet on Morris maze performance, oxidative stress, and inflammation in rats: contributions of maternal diet. Neurobiol. Dis. 35, 3–13. doi: 10.1016/j.nbd.2009.04.002
Wong-Goodrich, S. J. E., Glenn, M. J., Mellott, T. J., Blusztajn, J. K., Meck, W. H., and Williams, C. L. (2008). Spatial memory and hippocampal plasticity are differentially sensitive to the availability of choline in adulthood as a function of choline supply in utero. Brain Res. 1237, 153–166. doi: 10.1016/j.brainres.2008.08.074
Wu, A., Ying, Z., and Gomez-Pinilla, F. (2004). Dietary omega-3 fatty acids normalize BDNF levels, reduce oxidative damage, and counteract learning disability after traumatic brain injury in rats. J. Neurotrauma 21, 1457–1467. doi: 10.1089/neu.2004.21.1457
Wu, K. L. H., Wu, C. W., Tain, Y. L., Huang, L. T., Chao, Y. M., Hung, C. Y., et al. (2016). Environmental stimulation rescues maternal high fructose intake-impaired learning and memory in female offspring: its correlation with redistribution of histone deacetylase 4. Neurobiol. Learn. Mem. 130, 105–117. doi: 10.1016/j.nlm.2016.02.004
Wu, Z., Xiao, L., Wang, H., and Wang, G. (2021). Neurogenic hypothesis of positive psychology in stress-induced depression: adult hippocampal neurogenesis, neuroinflammation, and stress resilience. Int. Immunopharmacol. 97:107653. doi: 10.1016/j.intimp.2021.107653
Xavier, S., Soch, A., Younesi, S., Malik, S., Spencer, S. J., and Sominsky, L. (2021). Maternal diet before and during pregnancy modulates microglial activation and neurogenesis in the postpartum rat brain. Brain. Behav. Immun. 98, 185–197. doi: 10.1016/j.bbi.2021.08.223
Xu, Y., Ku, B., Cui, L., Li, X., Barish, P. A., Foster, T. C., et al. (2007). Curcumin reverses impaired hippocampal neurogenesis and increases serotonin receptor 1A mRNA and brain-derived neurotrophic factor expression in chronically stressed rats. Brain Res. 1162, 9–18. doi: 10.1016/j.brainres.2007.05.071
Xu, Y., Liu, Z., Xu, S., Li, C., Li, M., Cao, S., et al. (2022). Scientific evidences of calorie restriction and intermittent fasting for neuroprotection in traumatic brain injury animal models: a review of the literature. Nutrients 14:1431. doi: 10.3390/nu14071431
Yang, D., and Wan, Y. (2019). NR supplementation during lactation: benefiting mother and child. Trends Endocrinol. Metab. 30, 222–227. doi: 10.1016/j.tem.2019.02.004
Yang, Y., Yang, S., Liu, J., Feng, Y., Qi, F., and Zhao, R. (2019). DNA hypomethylation of GR promoters is associated with GR activation and BDNF/AKT/ERK1/2-Induced hippocampal neurogenesis in mice derived from folic-acid-supplemented dams. Mol. Nutr. Food Res. 63:1801334. doi: 10.1002/mnfr.201801334
Yau, S. Y., Li, A., and So, K. F. (2015). Involvement of adult hippocampal neurogenesis in learning and forgetting. Neural Plast. 2015:717958.
Zainuddin, M. S. A., and Thuret, S. (2012). Nutrition, adult hippocampal neurogenesis and mental health. Br. Med. Bull. 103, 89–114.
Keywords: adult neurogenesis, hippocampus, nutrients, diet, perinatal programming, gut microbiota
Citation: Melgar-Locatelli S, de Ceglia M, Mañas-Padilla MC, Rodriguez-Pérez C, Castilla-Ortega E, Castro-Zavala A and Rivera P (2023) Nutrition and adult neurogenesis in the hippocampus: Does what you eat help you remember? Front. Neurosci. 17:1147269. doi: 10.3389/fnins.2023.1147269
Received: 18 January 2023; Accepted: 06 February 2023;
Published: 23 February 2023.
Edited by:
Sumana Chakravarty, Indian Institute of Chemical Technology (CSIR), IndiaReviewed by:
Daniel Radford-Smith, University of Oxford, United KingdomCopyright © 2023 Melgar-Locatelli, de Ceglia, Mañas-Padilla, Rodriguez-Pérez, Castilla-Ortega, Castro-Zavala and Rivera. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Estela Castilla-Ortega, 
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†These authors have contributed equally to this work