Ilaria Bertocchi
Silvia Turroni
Fausto Chiazza- 1Department of Neuroscience Rita Levi Montalcini, University of Turin, Turin, Italy
- 2Neuroscience Institute - Cavalieri-Ottolenghi Foundation (NICO), Laboratory of Neuropsychopharmacology, Turin, Italy
- 3Unit of Microbiome Science and Biotechnology, Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy
- 4Department of Pharmaceutical Sciences, University of Eastern Piedmont, Novara, Italy
Editorial on the Research Topic
Nutritional modulation of central nervous system development, maintenance, plasticity, and recovery
There is no doubt about the negative impact of an unhealthy diet on Central Nervous System (CNS) development and homeostasis (Cordner and Tamashiro, 2015; Chiazza et al., 2021). Indeed, increasing evidence links modern diets (high in saturated fat, refined carbohydrates and processed foods) with cognitive and memory deficits, increased incidence of mood disorders and risk of neuroinflammation and neurodegenerative diseases (Gauci et al., 2022; Oberto et al., 2022).
The aim of the Frontiers in Neuroscience Research Topic (RT) “Nutritional modulation of central nervous system development, maintenance, plasticity, and recovery” was to spotlight the latest advances and research outputs highlighting the important role of nutrition on the CNS, during development, maintenance processes, plasticity, and recovery. We provide an overview of this RT, including 2 original research articles, 1 brief research report and 1 review article.
In this RT, Slomp et al. used a state-of-the-art imaging approach in mice to investigate the response of GABAergic neurons (Vgat positive) to diet in a key region regulating feeding behavior, the lateral hypothalamus (LH). Their main aim was to understand whether this neuronal population might be affected by a free-choice high-fat diet (fcHFD). Their findings revealed that fcHFD reduced overall LHVgat neuronal activity, but did not disrupt the increase in activity induced by sucrose consumption. Previous studies have reported diet-induced changes in LH activity and, interestingly, the same research group observed that fcHFD altered the response of glutamatergic LH neurons to sucrose drinking (Koekkoek et al., 2021). The results now reported demonstrate that short-term consumption of saturated fat can also influence the activity of the GABAergic neuronal population in the LH. However, it remains unclear how the fatty diet can dampen GABAergic tone without interfering with the ability of LHVgat neurons to recognize and react differently to sugar solution and water consumption. GABAergic neurons within the LH are influenced by different external and internal stimuli, including specific responses to taste reactivity, palatability and dopaminergic and opioid transmission. Given the heterogeneity of the LH GABAergic neuronal population, the mechanisms involved may therefore be multiple, complicated, and interconnected; this supports the case for further research.
In the context of this RT, microbiota-mediated effects of diet on brain performance and CNS homeostasis (via the so-called “gut-brain axis”) have been ascribed a leading role. Indeed, the community of more than 10 trillion microorganisms residing in our gastrointestinal tract can influence whole-body health by converting dietary components into bioactive small molecules that can enter the bloodstream, be further metabolized by the host, modulate the immune system, and reach distal organs (Turroni et al., 2018).
Salami and Soheili reviewed the available literature on the association of gut microbiota and probiotic supplements with behavioral, electrophysiological, biochemical, and histological aspects of the hippocampus (known to be involved in cognition, emotion, and anxiety). The 139 experimental studies and clinical trials included in their systematic review confirmed the ability of gut microbiota (and probiotics) to influence synaptic activity in hippocampal neural circuits and related behaviors. They also summarized the main molecular mechanisms known to date, including the production and modulation of neurotrophins, neurotransmitters and receptors, the regulation of intracellular molecular processes, the balance of pro-inflammatory/anti-inflammatory and pro-oxidative/anti-oxidative factors, and the preservation of histological stability of the hippocampus. However, as the authors pointed out, this field of research is still in its infancy and will require intensive future efforts to make practical advances in microbiota-based diagnosis and/or treatment of brain disorders.
The importance of continuing research into the gut-brain axis has been picked up by Freijy et al., who participated in this RT by evaluating the efficacy of probiotic supplements (a multi-species formulation of bifidobacteria and lactobacilli) on mental health. This formulation was tested in a randomized controlled trial (“The Gut Feelings”) against a high-prebiotic diet and a synbiotic (as a combination of probiotics and prebiotics) in 119 adults with moderate psychological distress (and low prebiotic intake). After 8 weeks of treatment, the authors found a reduction in total mood disturbance (the primary outcome) and improvements in anxiety, stress and sleep (secondary outcomes) only in the prebiotic group. While larger trials in both clinical and non-clinical populations are needed, their findings strongly support the importance of a healthy diet (rich in whole plant foods) as a simple and cost-effective means of promoting mental health.
In addition to diet, healthy physical habits are known to delay brain downfall, especially during aging. However, physical activity is not always feasible for elderly people, particularly in frail conditions such as after ischemic events. Therefore, an active research area is investigating therapeutic targets and strategies for developing exercise mimetics, particularly in CNS disorders.
On this basis, Ragni et al. have investigated whether dietary supplementation with a balanced essential amino acid mixture (BCAAem) influenced mitochondrial biogenesis and antioxidant response in the hippocampus of middle-aged mice compared to those evoked by treadmill exercise training. Here they have shown that BCAAem induced eNOS expression, mitochondrial biogenesis markers, and antioxidant genes in the mouse hippocampus to a degree comparable to that induced by exercise training. Furthermore, this diet supplementation promoted mitochondrial biogenesis in mouse cortical neurons in vitro and protected them from ischemic insult through mTOR and eNOS-mediated mechanism(s). This last finding is particularly interesting as the risk of ischemic stroke onset is known to be strongly increased by a metabolic derangement, and many pharmacological strategies have been attempted in this regard (Chiazza et al., 2018). Thus, also in this field, future investigations using in vivo models of cerebral ischemia are needed to deepen the role of BCAA-based metabolic modulators in stroke prevention or as a valuable aid in multidisciplinary post-stroke rehabilitation in humans.
As highlighted by this RT, a better understanding of how diet may influence CNS homeostasis, including through gut-brain signaling, is pivotal to provide us with effective tools to address unhealthy dietary behaviors and associated brain disorders.
Author contributions
IB: Writing—original draft, Writing—review & editing. ST: Writing—original draft, Writing—review & editing. FC: Writing—original draft, Writing—review & editing.
Funding
The author(s) declare that no financial support was received for the research, authorship, and/or publication of this article.
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.
The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.
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References
Chiazza, F., Bondi, H., Masante, I., Ugazio, F., Bortolotto, V., Canonico, P. L., et al. (2021). Short high fat diet triggers reversible and region specific effects in DCX+ hippocampal immature neurons of adolescent male mice. Sci. Rep. 11, 21499. doi: 10.1038/s41598-021-01059-y
Chiazza, F., Tammen, H., Pintana, H., Lietzau, G., Collino, M., Nyström, T., et al. (2018). The effect of DPP-4 inhibition to improve functional outcome after stroke is mediated by the SDF-1α/CXCR4 pathway. Cardiovasc. Diabetol. 17, 1–13. doi: 10.1186/s12933-018-0702-3
Cordner, Z. A., and Tamashiro, K. L. K. (2015). Effects of high-fat diet exposure on learning and memory. Physiol. Behav. 152, 363–371. doi: 10.1016/j.physbeh.2015.06.008
Gauci, S., Young, L. M., Arnoldy, L., Lassemillante, A. C., Scholey, A., Pipingas, A., et al. (2022). Dietary patterns in middle age: effects on concurrent neurocognition and risk of age-related cognitive decline. Nutr. Rev. 80, 1129–1159. doi: 10.1093/nutrit/nuab047
Koekkoek, L. L., Slomp, M., Castel, J., Mutersbaugh, M., Linville, I., Serlie, M. J., et al. (2021). Disruption of lateral hypothalamic calorie detection by a free choice high fat diet. FASEB J. 35, 9. doi: 10.1096/fj.202100762R
Oberto, A., Bertocchi, I., Longo, A., Bonzano, S., Paterlini, S., Meda, C., et al. (2022). Hypothalamic NPY-Y1R interacts with gonadal hormones in protecting female mice against obesity and neuroinflammation. Int. J. Mol. Sci. 23, 6351. doi: 10.3390/ijms23116351
Keywords: nutrition, brain, gut-brain axis, cognition, mood
Citation: Bertocchi I, Turroni S and Chiazza F (2023) Editorial: Nutritional modulation of central nervous system development, maintenance, plasticity, and recovery. Front. Neurosci. 17:1332191. doi: 10.3389/fnins.2023.1332191
Received: 02 November 2023; Accepted: 07 November 2023;
Published: 17 November 2023.
Edited and reviewed by: Paul Forsythe, University of Alberta, Canada
Copyright © 2023 Bertocchi, Turroni and Chiazza. 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: Fausto Chiazza, fausto.chiazza@uniupo.it