Written by Liang Wenquan

Editor in charge ︱ Wang Sizhen

Editor︱Yang Binwei

Schizophrenia (SCZ) is a common type of severe mental illness with a prevalence of about 1%, involving abnormalities such as disorders of neural circuits and synaptic plasticity

Recently, Zhao Cunyou's team from the Medical Genetics Department of Southern Medical University and Chen Rongqing's team from the Department of Neurobiology published online in Science Advances entitled "Loss of schizophrenia-related miR-501-3p in mice impairs sociability and memory by enhancing mGluR5-mediated glutamatergic Transmission" research paper describing the epigenetic loss of differentially expressed miR-501-3p in schizophrenia identical twins induces social and memory behavioral abnormalities in mice by regulating excitatory glutamatergic hypertransmission The mechanism provides new clues for the etiology study of schizophrenia

This study is devoted to discovering the miRNAs that mediate differences in the risk of schizophrenia among identical twins, and to further study the molecular network of their regulation

Figure 1.

(Image source: Liang W, et al.

.

In order to further study the pathogenic mechanism and molecular regulatory network of miRNAs, the authors constructed Mir501 knockout mice through the FLEX strategy (Figure 2A).

Figure 3.

(Image source: Liang W, et al.

Conclusion and discussion, inspiration and prospect In conclusion, this study screened miRNAs associated with schizophrenia susceptibility by using the precious clinical resource of monozygotic twins with schizophrenia, and further through two independent studies and Decreased miR-501-3p expression in the peripheral blood of schizophrenia patients was confirmed in the schizophrenia population in southern China, and cross-species studies were performed using mice, social deficits, memory impairment, and sensory-gated channels were developed in Mir501 KO mice Behavioral phenotypes such as abnormality, and cellular phenotypes such as abnormal neuronal structure, abnormal excitability, and hyperglutamatergic transmission; using Nestin-Cre mice to restore Mir501 expression in the central nervous system improves the above abnormal phenotypes, further supporting the results from The results of peripheral blood studies of patients showed that down-regulation of miR-501-3p expression was associated with susceptibility to schizophrenia
.

It was verified by proteomics and cytology that mGluR5 is one of the downstream target genes of miR-501-3p.
The negative allosteric regulators of mGluR5, MTEP and NMDAR antagonist AP5, can improve the abnormal phenotype caused by the loss of miR-501 expression
.

These findings suggest that downregulation of miR-501-3p expression increases the risk of schizophrenia through mGluR5-mediated hyperglutamatergic transmission, and utilization of MTEP ameliorates the abnormal phenotype implicated by loss of miR-501-3p expression We, in the future, can achieve better clinical therapeutic effects through mGluR5 allosteric modulators with more specificity and lower side effects
.

This study is the first to propose an epigenetic regulatory mechanism that miR-501-3p associates with glutamatergic transmission through mGluR5, providing new clues for the etiology of schizophrenia
.

Although the proportion of male and female clinical samples in this study is balanced, because Mir501 is located on the X chromosome, the subsequent research data involving mice are all from male mice.
In the next work, we will further verify our results in female mice.
Experimental conclusion: At the same time, in twin samples and sporadic samples, we also found that two other miRNAs were down-regulated in schizophrenia-related expression.
We will further verify the relationship between these two miRNAs and schizophrenia in the next work
.

Original link: https://doi.
org/10.
1126/sciadv.
abn7357

The School of Basic Medical Sciences of Southern Medical University is the main completion unit and communication unit of the research.
Prof.
Zhao Cunyou from the Teaching and Research Section of Medical Genetics and Prof.
Chen Rongqing from the Teaching and Research Section of Neurobiology are the co-corresponding authors.
Ph.
D.
and master student Wang Yunqian majoring in genetics are the co-first authors of this article
.

The work was supported by the Third People's Hospital of Zhongshan City, the Brain Hospital Affiliated to Guangzhou Medical University, the Guangdong Provincial Mental Health Center, the Zhujiang Hospital Affiliated to Southern Medical University, the Key Laboratory of Mental Health Research of the Ministry of Education, the Guangdong-Hong Kong-Macao Greater Bay Area Brain Science and Brain-inspired The research center, Guangdong Provincial Key Laboratory of Major Mental Illness Research, Guangdong Provincial Genetic Testing Engineering Technology Research Center and other units, as well as the National Natural Science Foundation of China and the Guangdong Provincial Department of Science and Technology and other departments project funding
.

About the author (swipe up and down to read) 

Professor Zhao Cunyou is currently the director of the Medical Genetics Teaching and Research Section of the School of Basic Medicine, Southern Medical University
.

He is mainly engaged in the study of epigenetic regulation mechanism of complex phenotypic variation in human genetic diseases.
He has published more than 40 SCI papers in Science Advances, Molecular Psychiatry, American Journal of Human Genetics, Schizophrenia Bulletin,
etc.

The research group mainly focuses on the mechanism of epigenetic modification mediating the interaction of genetic and environmental factors in the development of psychosis (schizophrenia and bipolar disorder)
.

Taking twin families as objects, study allele-specific DNA modification and RNA expression, microRNA, long non-coding RNA, etc.
involved in the pathogenesis of psychosis; at the same time, by constructing peripheral blood-derived iPSCs, two-dimensional neuron and three-dimensional brain-like Organ differentiation, combined with gene editing technology, to carry out research on the functional mechanism of susceptibility genes involved in the development of the nervous system
.

The research group recruits postdoctoral fellows all the year round.
We look forward to and welcome you to join us!

Selected past articles

【1】J Infect︱Wang Yifei's team revealed that the highly expressed gene MAMDC2 in Alzheimer's disease microglia positively regulates the innate antiviral response to neurotropic virus infection

【2】Sci Adv︱Xia Kun/Shen Yiping/Guo Hui Reveal the relationship between key regulatory genes of stress granules and neurodevelopmental disorders

【3】Cell Prolif︱Lai Liangxue/Zhang Kun/Zou Qingjian team successfully constructed a technical system for safe and efficient directional induction of motor neurons in vivo

【4】Nat Commun︱Peng Yueqing's team discovered a new brain area that controls non-REM sleep

【5】eClinicalMedicine︱Wang Qing’s team reported Parkinson’s disease dementia related index determination: quantitative EEG, serum metabolism and inflammation

【6】Cell Biosci | Wang Yongjun's research group reveals the molecular mechanism of D-type dopachrome isomerase-mediated inflammatory response in injured spinal cord

【7】Neuron｜Hu Yang's group revealed a large number of genes that promote optic nerve regeneration and their significant neuroprotective effects in glaucoma mice

【8】Cereb Cortex︱Zhang Yuxuan's research group reveals the neurophysiological evidence of task modulation in speech processing

[9] Trends Cogn Sci︱Jiang Qiu team writes opinion articles on creative problem solving in knowledge-rich fields

【10】Front Aging Neurosci︱Hongmei Yu's team constructed a hierarchical multi-classification diagnosis framework for AD based on imaging features and clinical information

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End of this article