Lian‑Hong Lin1,2 · Wei‑Min Li1,2 · Qian‑Yun Wu1,2 · Shuang‑Yan Li1,2 · Xu‑Xuan Ma1,2 · Yuan Xu1,2 · Si‑Fu Deng1,2 · Bin Zhang1,2  · Ji‑Hong Liu1,2

1 Department of Psychiatry, Sleep Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China 

2 Key Laboratory of Mental Health of the Ministry of Education, Southern Medical University, Guangzhou 510515, China

Abstract

Schizophrenia (SCZ) is a severe mental illness influenced by gene-environment interactions (GEI). However, little is known about how GEI mediates SCZ. The present study aimed to examine the underlying mechanism of SCZ mediated by GEI. We found that a single environmental factor (two-week adolescent social isolation) or genetic factor (the heterozygous Rims1 knockout mice) did not induce SCZ-like behaviors. Interestingly, two-week adolescent social isolation successfully caused SCZ-like behaviors in heterozygous Rims1 knockout mice, which can be rescued by anti-SCZ drugs. RNA-seq analysis further revealed that synaptic vesicle-related biological processes and target genes were enriched in the hippocampus of GEI animal model mice, which was accompanied by disturbed excitatory synaptic neurotransmission. Finally, the Nrg1 gene was decreased in our RNA-seq analysis, and supplementation of Nrg1 ameliorated SCZ-like behaviors in heterozygous Rims1 socially isolated mice. Our findings establish a novel GEI animal model and offer a potential therapeutic target in the treatment of SCZ.

Keywords

Schizophrenia; Gene-environment interactions; Animal model; RNA-seq; Nrg1

[SpringerLink]