/   Home   /   Newsroom   /   Research News

Inhibition of PDE10A Rescues Impaired Social Behavior with Partial Loss of MIR137 in Mice, Study

Nov 07, 2018     Email"> PrintText Size

Autism spectrum disorder (ASD) is a group of neuropsychiatric disorders characterized by restricted interests, repetitive behaviors, and difficulty with social communication and interaction.

The molecular mechanisms underlying the pathogenesis of ASD are poorly understood. Previous meta-analyses combining genome-wide association studies identified MIR137 as a candidate ASD gene. However, whether the dysregulation of miR-137 leads directly to the phenotypes associated with ASD remains to be determined.

In a recent study published in Nature Neuroscience, an international research team led by Drs. TENG Zhaoqian and CHEN Dahua from the Institute of Zoology, Chinese Academy of Sciences, together with Dr. JIN Peng from the Department of Human Genetics, Emory University School of Medicine, generated a miR-137 conditional allele to examine the impact of miR-137 loss of function in vivo.

They found that partial loss of miR-137 in mice leads to repetitive behaviors, impaired sociability and social novelty preference, and deficits in learning and memory.

Scientists then observed that many upregulated ASD candidate genes were significantly associated with miR-137 predicted targets by combining large-scale proteomic analyses with gene expression profiling.

Among the targets with most-changed protein levels, phosphodiesterase 10a (PDE10A) is significantly elevated in miR-137 heterozygous knockout mice.

Inhibition of PDE10A by either short hairpin RNA (sh-Pde10a) or specific inhibitor (papaverine) ameliorates abnormal behaviors associated with the partial loss of miR-137.

Given the known genetic association between MIR137 and neuropsychiatric disorders, their findings provide direct evidence that dysregulation of miR-137 directly contributes to the molecular pathogenesis of neuropsychiatric disorders.

Importantly, this research suggests that PDE10A should be a potential therapeutic target to a subgroup of ASD associated with the partial loss of MIR137.

 

MiR-137-mediated regulation in ASD candidate genes interactome (A), and rescue effect of PDE10A inhibitor in miR-137 heterozygous knockout mice (B, C, D, E) (Image by CHENG Ying) 

(Editor: ZHANG Nannan)

Contact

TENG Zhaoqian

Institute of Zoology

Phone:
E-mail: tengzq@ioz.ac.cn

Related Articles

schizophrenia;autism spectrum disorder;ASD;MIR-137

'Master Key' Gene Has Links to both ASD and Schizophrenia

Nov 06, 2018

Recent studies of complex brain disorders such as schizophrenia and autism spectrum disorder (ASD) have identified a few "master keys," risk genes that sit at the center of a network of genes important for brain function. Researchers at Emory and the C...

working memory;autism spectrum disorder;ASD;WM impairments;meta-analysis;moderator

Scientists Demonstrate Working Memory Impairments in Individuals with Autism Spectrum Disorders

Oct 26, 2017

Prof. Raymond Chan, Dr. WANG Ya and team members from Institute of Psychology of the Chinese Academy of Sciences have conducted a meta-analsis study to examine severity of WM impairments in individuals with ASD and evaluated the potential moderating va...

Contact Us

Copyright © 2002 - Chinese Academy of Sciences