Sino-foreign cooperation research reveals the regulation mechanism of mental illness

Author: Cheng Wei Jia Release Date: 2018-11-07

Recently, the Institute of Zoology, Chinese Academy of Sciences, Emory University School of Medicine, Chinese Academy of Sciences Stem Cell and Regenerative Medicine Innovation Institute, University of Chinese Academy of Sciences, St. Jude Children's Research Hospital, Southeast University and other institutions, for the first time provided miR-137 Deletion of in vivo experimental evidence leading to mental illness further reveals the molecular regulatory mechanisms of miR-137-deficient psychiatric disorders. The study was published online November 5 in Nature Neuroscience.

Mental illness is a neurological disorder of mental activity such as behavior, cognition, learning, and emotion. At present, the understanding of its etiology is still unclear and lacks effective therapeutic drugs.

In recent years, a number of independent genome-wide association studies have found that mutations in the MIR137 gene coding region (1p21.3, encoding small molecule non-coding RNA miR-137) on chromosome are closely related to the occurrence of schizophrenia.

"In our early research work, techniques such as lentivirus and retrovirus with gene overexpression and knockdown have confirmed that miR-137 plays an important role in neurogenesis, neuronal maturation, prominent plasticity, learning and memory, etc. Chen Dahua, a researcher and author of the Institute of Zoology of the Chinese Academy of Sciences, told the Journal of the Chinese Academy of Sciences, but the scientific problem of whether the loss of miR-137 has an impact on individual mental activity, its influence, and how it affects has yet to be resolved.

After years of joint research, the researchers constructed miR-137 systemic knockout mice and neurological specific knockout mouse models. It was found that homozygous mice with miR-137 systemic knockout or neurological specific knockout died within a few weeks after birth. Heterozygous miR-137 knockdown mice can survive to adulthood. Cell level detection revealed that partial deletion of miR-137 caused phenotypic abnormalities in synaptic pruning, synaptic plasticity, and synaptic protein expression in mice.

The study also found that heterozygous miR-137 knockdown mice showed significant mental disorders such as stereotyped repetitive behavior, decreased social ability, impaired social preferences, and learning and memory deficits. In order to reveal the molecular mechanism behind these phenotypes, the researchers used proteomics, transcriptome, molecular biology, biochemistry and other methods to identify a key target gene of miR-137, Pde10a (phosphodiesterase 10a). By injecting mice with Pde10a specific inhibitor (papaverine) or short hairpin RNA virus (sh-Pde10a), the heterozygous miR-137 knockdown mice have a very rigid stereotype, social ability, learning and memory function. Good improvement.

"These findings suggest that PDE10A inhibitors such as papaverine may be potential drugs for miR-137-deficient psychiatric disorders." Teng Zhaogan, a researcher at the Institute of Zoology, Chinese Academy of Sciences, said that future research efforts will shift to miR-137-deficient mouse models and humans. Techniques such as pluripotent stem cells and brain-like brains provide insights into the pathogenesis of miR-137-deficient psychiatric disorders, and evaluate and develop interventions to treat psychotic disorders.

Source: Science Network