Anna Maria Lavezzi
Marco Colizzi
Pamela J. Lein- 1“Lino Rossi” Research Center for the Study and Prevention of Unexpected Perinatal Death and SIDS, Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy
- 2Unit of Psychiatry, Department of Medicine (DAME), University of Udine, Udine, Italy
- 3Department of Molecular Biosciences, UC Davis School of Veterinary Medicine, University of California, Davis, Davis, CA, United States
Editorial on the Research Topic
Advances in understanding the pathogenetic mechanisms of neurodevelopmental disorders and neurodegenerative disease — The environment as a putative risk factor
Introduction
Neurodevelopmental disorders are generally influenced by not only genetic, but also intrauterine and extrauterine factors that affect the fetal-maternal environment and/or brain development that continues after birth (1). Specific genetic polymorphisms may increase susceptibility to environmental factors that alter the trajectory of brain development via diverse molecular mechanisms (2). In particular, pre- and post-natal exposure to neurotoxic metals, pesticides, persistent organic pollutants, and other chemicals is increasingly recognized as involved in the pathogenesis of neurodevelopmental disorders, such as autism, deficiency attention/hyperactivity disorders, and even fetal and infant death, including SIUDS (Sudden Unexplained Intrauterine Death Syndrome) and SIDS (Sudden Infant Death Syndrome) (3–9).
Similar evidence has been found also for neurodegenerative disorders such as Parkinson's, Alzheimer's disease, and chronic multiple sclerosis (10–12). In fact, especially in the context of specific genetic vulnerability, exposure to such environmental factors across the lifespan increases the likelihood of neurodegenerative processes. Combining research outputs from studies of both neurodevelopment and neurodegeneration may help advance our understanding of the complex phenomena that modulate brain structure and function throughout life, with implications for health and disease.
Thus, it is essential to study the ethio-pathogenetic and anatomo-pathological aspects of neurodevelopmental disorders and neurodegenerative disease with particular attention to the study of specific biomarkers useful for diagnostic and prognostic purposes.
The goal of the Research Topic “Advances in understanding the pathogenetic mechanisms of neurodevelopmental disorders and neurodegenerative disease — The environment as a putative risk factor” was to collect contributions from expert authors in order to advance the state of knowledge regarding the pathogenetic mechanisms by which various factors, including drugs, diet, genetic, and environmental factors, interact to increase individual risk for neurological disorders and diseases across the lifespan.
This Research Topic was proposed in particular to focus on the following subtopics:
• Genetic background that may increase susceptibility to environmental factors that alter nervous system development
• Molecular and neuropathological features of neurological disease across the lifespan
• Approaches for identifying specific genetic substrates and environmental factors that alter brain development to cause disease
• Mechanisms by which genetic and environmental factors interact to increase risk of neurological disease
• Neuropathology of unexplained perinatal deaths, considering also the interaction between environmental risk factors and brain developmental defects
• Proposal of evidence-based prevention and management strategies to decrease the incidence of these pathologies.
Published articles
In order to summarize the contributions to this Research Topic, we have grouped the articles in two main sections: one dedicated to new perspectives useful both for preventive and diagnostic purposes of various neurological disorders and a second focused on new biomarkers which can help in predicting Alzheimer's and Parkinson's diseases.
Section 1- Original perspectives on pathogenesis of sleep disorders, cognitive alterations and neurodegenerative processes
The articles are distributed in the following subsections:
(a) New indicators of neurodegenerative processes
• Through a meta-analysis approach, Zhang L. et al. highlighted a positive association between exposure to first-generation antiepileptic drugs (such as valproate, carbamazepine, and clonazepam) and increased risk of dementia.
• Li W. et al., in an original study found that dietary inflammation and blood inflammation indexes are negatively associated with cognitive function in an elderly American population.
• The experimental research of Li G.-S. et al. explored the ultrastructural pathological changes of the neurovascular unit (NVU), a structural and functional complex that plays an important role in the coupled interaction between neural activity and microcirculation, and consequently in the pathophysiological mechanism of many cerebral disorders. The study disclosed the presence of NVU destruction in the development stage of the cervical spondylotic myelopathy (CSM), the most common cervical spinal cord disorder among the elderly population.
(b) Involvement of environmental factors in neurological disorders
• Calderón-Garcidueñas et al. envisaged how exposures to high concentrations of particulate matter (PM2.5), ultrafine particulate and industrial nanoparticles, can damage the nervous system dating back to in prenatal life, playing a significant role in the development of neurodegenerative processes and sleep disorders.
• The adverse impact of exposure to neurotoxic metal mixtures on brain connectivity was illustrated by Invernizzi et al. through neuroimaging studies on a wide set of young people. They demonstrate that various metal mixtures may alter the brain development by modifying the global and local connectivity. These changes may potentially lead to alterations in cognition and neurobehavior in adolescents and young adults.
• Damage from toxic metals was also demonstrated by Vegard et al.. The aim of this study was to investigate whether early-life exposure to toxic metals and essential elements can adversely affect nervous system development. These authors demonstrated an association between second trimester maternal blood levels of copper and manganese and increased risk of Cerebral Palsy, which is the most common motor disability in childhood, the causes of which are currently only partly known.
• The study of Humphreys and Valdés Hernández, based on a systematic review and meta-analysis, supports the hypothesis that prenatal polycyclic aromatic hydrocarbon exposure negatively affects cognitive function and increases the risk of neurodegeneration in humans.
• Spencer et al. proposed an intensive analysis of published geographic clusters of conjugal cases, single-affected twins, and young-onset cases of Amyotrophic Lateral Sclerosis (ALS), to identify which environmental factors may trigger motor neuron disease. The study highlights that exposure to naturally occurring or synthetic hydrazine-related chemicals, acting alone or in the presence of a genetic susceptibility, is associated with the development of clinical ALS.
Section 2- New diagnostic parameters for the early identification of individuals at risk of Parkinson's and Alzheimer's diseases
• New biomarkers for predicting the occurrence of Parkinson's disease (PD) have been highlighted by Zhang P. et al. They used bioinformatics analysis of the immune system to show that the analysis of four immune infiltration-related genes (precisely SYT1, NEFM, GAP43, and GRIA1) identified individuals at risk of PD before the onset of motor symptoms.
• The relation between hypertension and increased risk of AD has been underlined by Sáiz-Vazquez et al. in original research based on the analysis of information predominantly obtained by meta-analyses of primary studies worldwide.
• In an explorative study, Tsai et al. investigated the associations between sleep parameters measured using polysomnography and plasma levels of selected biomarkers of neurodegenerative diseases in patients with suspected obstructive sleep apnea (OSA) to assess the relationships between sleep disorders and the risk of Alzheimer's disease development. The results reveal that individuals at high-risk have significantly higher mean values for various indices of sleep-disordered breathing and arousal responses than those at low-risk.
Conclusions
We believe that the above contributions, although heterogeneous in their approach, collectively broaden the current knowledge on the pathogenetic mechanisms of neurodevelopmental disorders and neurodegenerative diseases, which often involves complex interactions between genetic and non-genetic factors, including exposure to environmental contaminants. In conclusion, we hope these articles will prove useful for improving current diagnostic criteria and preventive strategies and also for providing impetus for further research in the field of this Research Topic.
Author contributions
AL: Conceptualization, Data curation, Validation, Writing—original draft, Writing—review and editing. MC: Conceptualization, Data curation, Validation, Writing—original draft. PL: Conceptualization, Supervision, Validation, Writing—original draft, Writing—review and editing.
Acknowledgments
The Research Topic Editors express sincere gratitude to the authors who accepted the invitation to contribute to this collection and the reviewers for their significant comments, so elevating the quality of the submitted articles. Finally, they thank Frontiers and, in particular, the Editorial Office for the essential support.
Conflict of interest
MC has been a consultant/advisor to GW Pharma Limited, GW Pharma Italy SRL, and F. Hoffmann-La Roche Limited outside of this work.
The remaining 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.
Publisher's note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.
References
1. Connors SL, Levitt P, Matthews SG, Slotkin TA, Johnston MV, Kinney HC, et al. Fetal mechanisms in neurodevelopmental disorders. Pediatr Neurol. (2008) 38:163–76. doi: 10.1016/j.pediatrneurol.2007.10.009
2. Miguel PM, Pereira LO, Silveira PP, Meaney MJ. Early environmental influences on the development of children's brain structure and function. Dev Med Child Neurol. (2019) 61:1127–33. doi: 10.1111/dmcn.14182
3. Andrade VM, Aschner M, Marreilha dos Santos AP. Neurotoxicity of metal mixtures. Adv Neurobiol. (2017) 18:227–65. doi: 10.1007/978-3-319-60189-2_12
4. López-Merino E, Cuartero MI, Esteban JA, Briz V. Perinatal exposure to pesticides alters synaptic plasticity signaling and induces behavioral deficits associated with neurodevelopmental disorders. Cell Biol Toxicol. (2022). doi: 10.1007/s10565-022-09697-2
5. Karimi P, Kamali E, Mousavi SM, Karahmadi M. Environmental factors influencing the risk of autism. J Res Med Sci. (2017) 22:27. doi: 10.4103/1735-1995.200272
6. Bernardina Dalla MD, Ayala CO, Cristina de Abreu Quintela Castro F, Neto FK, Zanirati G, Cañon-Montañez W, et al. Environmental pollution and attention deficit hyperactivity disorder: a meta-analysis of cohort studies. Environ Pollut. (2022) 315:120351. doi: 10.1016/j.envpol.2022.120351
7. De Felice A, Ricceri L, Venerosi A, Chiarotti F, Calamandrei G. Multifactorial origin of neurodevelopmental disorders: approaches to understanding complex etiologies. Toxics. (2015) 3:89–129. doi: 10.3390/toxics3010089
8. Gatti AM, Montanari S, Ferrero S, Lavezzi AM. Silver nanoparticles in the fetal brain: new perspectives in understanding the pathogenesis of unexplained stillbirths. Nanomedicine. (2021) 16:265–74. doi: 10.2217/nnm-2020-0391
9. Dales R, Burnett RT, Smith-Doiron M, Stieb DM, Brook JR. Air pollution and sudden infant death syndrome. Pediatrics. (2004) 113:1798. doi: 10.1542/peds.113.6.e628
10. Ball N, Teo WP, Chandra S, Chapman J. Parkinson's disease and the environment. Front Neurol. (2019) 10:218. doi: 10.3389/fneur.2019.00218
11. Das N, Raymick J, Sarkar S. Role of metals in Alzheimer's disease. Metab Brain Dis. (2021) 36:1627–39. doi: 10.1007/s11011-021-00765-w
Keywords: neurodevelopmental disorders, neurodegenerative disease, environmental factors, Parkinson's disease, Alzheimer's disease, sleep disorders
Citation: Lavezzi AM, Colizzi M and Lein PJ (2023) Editorial: Advances in understanding the pathogenetic mechanisms of neurodevelopmental disorders and neurodegenerative disease — The environment as a putative risk factor. Front. Neurol. 14:1259772. doi: 10.3389/fneur.2023.1259772
Received: 16 July 2023; Accepted: 25 July 2023;
Published: 03 August 2023.
Edited and reviewed by: Bruce Miller, University of California, San Francisco, United States
Copyright © 2023 Lavezzi, Colizzi and Lein. 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: Anna Maria Lavezzi, anna.lavezzi@unimi.it