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MicroRNA therapeutics for stratified treatment of Schizophrenia

ABSTRACT: Schizophrenia (SZ) is a devastating psychiatric illness affecting 1% of the world population. In addition to genetic predisposition, environmental factors contribute to the risk for developing SZ. Such genome environment interactions frequently activate epigenetic and epitranscriptomic mechansims. There are emerging evidence that genetic and environmental risk factors merge at the level of microRNA expression, which are discussed as biomarker and therapeutic target in various disorders including neuropsychiatric diseases. In this study we analyzed the blood microRNAome of healthy individuals and SZ patients via small RNA sequencing. By combining these data with a corresponding analysis of post-mortem human brain tissue, we identify one candidate microRNA that is down-regulated in patients. Moreover, its expression is significantly correlated to disease phenotypes. Manipulation of this microRNAs in mouse prefrontal cortex causes schizophrenia-like phenotypes. Functional analysis revealed the cellular processes affected by this microRNA and allowed us to develop an arsenal of RNA-based therapeutic approaches that are able to ameliorate molecular disease phenotypes in mouse and human-based cellular systems as well as the behavioral phenotypes. In conclusion, we identify a novel microRNA as target for stratified RNA-therapeutics in schizophrenia.

ORGANISM(S): Mus musculus

PROVIDER: GSE224142 | GEO | 2024/03/26

REPOSITORIES: GEO

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