Cai Qi
Lu Wang2*
Yong Lu- 1Department of Neuroscience, Yale School of Medicine, New Haven, CT, United States
- 2Department of Neurosciences, School of Medicine, University of California, San Diego, La Jolla, CA, United States
- 3Department of Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- 4Division of Endocrinology and Metabolism, School of Medicine, University of California, San Diego, La Jolla, CA, United States
Editorial on the Research Topic
Molecules, environments, and neurological disorders
Both nature and nurture play significant roles in determining the likelihood of normal or abnormal development of the individuals. Recent clinical genetic studies have identified numerous variants associated with neurological disorders, providing potential genetic causes which can be further explored to understand the underlying pathological mechanisms. Additionally, twin studies in 1999 highlighted the contribution of non-genetic factors in development of neurological disorders (1, 2). Indeed, the genetic variants and genomic homeostasis can be perturbed by environmental molecules, eliciting diseases pathogenesis with few changes in the genome (3). For example, there is compelling evidence from rodents that metabolic changes induced by nutrition intake in parentals has long-lasting effects on developmental and behavioral phenotypes of their offsprings (4–7). Therefore, gaining a better understanding of the interactions between environmental molecules and genetic/genomic factors will benefit both preventive medicine and patients by correcting the abnormal processes without putting the integrity of genome at risk.
The brain receives information from external stimulation as well as internal states and thus is affected by environments heavily. Under most circumstances, environmental stimulation causes neurological phenotypes via gene expression by acting on the epigenome. The environmental factors include chemicals (8), hormones (9), and neurotransmitters. At the embryonic stage, the maternal environment is crucial for the proper development of the nervous system of the progenies. Zika causes microcephaly after maternal infection (10, 11). It has also been reported that exposure of pollutant induced maternal immune response which will undermine the microglia function and synaptic development (12). In a mini-review, Doi et al. summarized the latest studies on maternal immune activation and drug usage on the development of psychiatric disorders such as autism spectrum disorder, and schizophrenia, with a focus on synapse development related molecules, neurotransmitter, and hormone changes. Endocrine-disrupting compounds have been reported to elicit diseases through epigenetic modifications (13). In a research article by Martinez et al., they reported that embryonic exposure to thyroid hormone causes autism spectrum-like behavior in the third-generation wild-type mouse through epigenetic modification of autistic genes. Their study revealed how environmental exposure was “recorded” and passed through generations. With the advances of sequencing technology and the lowering cost, more and more disorders will be dissected at an otherwise unattainable resolution. Recently, we have started to appreciate the contribution of more and more variants in probands of various disorders. Among these variants, a proportion are de novo. Genetic analysis will enable us to uncover when and where these variants were generated in the lineage. In this Research Topic, Vado et al. reported the distribution of variants in families with inactivating PTH/PTHrP signaling disorder type2. Zhang et al. reported a novel mutation in the GLI2 gene and reviewed other causative mutations. The accumulation of such kind of knowledge will accelerate the application of precise medicine as suggested by Gilis-Januszewska et al. who used Cushing syndrome as an example. We are expecting continued progress in this field and looking forward to the clinical applications.
Author contributions
CQ, LW, and CJ write the manuscript. All authors consent on the contents of the manuscript. All authors contributed to the article and approved the submitted version.
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
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. Tanner CM, Ottman R, Goldman SM, Ellenberg J, Chan P, Mayeux R, et al. Parkinson disease in twins: an etiologic study. JAMA (1999) 281:341–6. doi: 10.1001/jama.281.4.341
2. Shrestha S, Parks CG, Umbach DM, Richard-Barber M, Hofman JN, Chan P, et al. Pesticide use and incident Parkinson’s disease in a cohort of farmers and their spouses. Environ Res (2020) 191:110186. doi: 10.1016/j.envres.2020.110186
3. Peters A, Nawrot TS, Baccarelli AA. Hallmarks of environmental insults. Cell (2021) 184:1455–68. doi: 10.1016/j.cell.2021.01.043
4. Gluckman PD, Hanson MA, Bateson P, Beedle AS, Law CM, Bhutta ZA, et al. Towards a new developmental synthesis: adaptive developmental plasticity and human disease. Lancet (2009) 373:1654–7. doi: 10.1016/S0140-6736(09)60234-8
5. Bordeleau M, Comin CH, Cossio LFd, Lacabanne C, Freitas-Andrade M, Ibanez FG, et al. Maternal high-fat diet in mice induces cerebrovascular, microglial and long-term behavioural alterations in offspring. Commun Biol (2022) 5:26. doi: 10.1038/s42003-021-02947-9
6. Fernandes DJ, Spring S, Roy AR, Qiu LR, Yee Y, Nieman BJ, et al. Exposure to maternal high-fat diet induces extensive changes in the brain of adult offspring. Transl Psychiatry (2021) 11:149. doi: 10.1038/s41398-021-01274-1
7. Ng SF, Lin RCY, Laybutt DR, Barres R, Owens JA, Morris MJ. Chronic high-fat diet in fathers programs beta-cell dysfunction in female rat offspring. Nature (2010) 467:963–6. doi: 10.1038/nature09491
8. Wheeler MA, Jaronen M, Covacu R, Zandee SEJ, Scalisi G, Rothhammer V, et al. Environmental control of astrocyte pathogenic activities in CNS inflammation. Cell (2019) 176:581–596 e518. doi: 10.1016/j.cell.2018.12.012
9. Kraft FH, Crino OL, Buchanan KL. Developmental conditions have intergenerational effects on corticosterone levels in a passerine. Horm Behav (2021) 134:105023. doi: 10.1016/j.yhbeh.2021.105023
10. Johansson MA, Mier-y-Teran-Romero L, Reefhuis J, Gilboa SM, Hills SL. Zika and the risk of microcephaly. N Engl J Med (2016) 375:1–4. doi: 10.1056/NEJMp1605367
11. Rasmussen SA, Jamieson DJ, Honein MA, Petersen LR. Zika virus and birth defects–reviewing the evidence for causality. N Engl J Med (2016) 374:1981–7. doi: 10.1056/NEJMsr1604338
12. Block CL, Eroglu O, Mague SD, Smith CJ, Ceasrine AM, Sriworarat C, et al. Prenatal environmental stressors impair postnatal microglia function and adult behavior in males. Cell Rep (2022) 40:111161. doi: 10.1016/j.celrep.2022.111161
Keywords: environment, molecules, genetics, epigenetics, neurological disorders
Citation: Qi C, Wang L, Lu Y and Jin C (2023) Editorial: Molecules, environments, and neurological disorders. Front. Endocrinol. 14:1244800. doi: 10.3389/fendo.2023.1244800
Received: 23 June 2023; Accepted: 07 August 2023;
Published: 28 August 2023.
Edited and Reviewed by:
Hubert Vaudry, Université de Rouen, FranceCopyright © 2023 Qi, Wang, Lu and Jin. 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: Cai Qi, cai.qi@yale.edu; Lu Wang, luw060@health.ucsd.edu; Chunyu Jin, c3jin@health.ucsd.edu; Yong Lu, 18917762053@163.com