Early Life Stress Alters Gene Expression and Cytoarchitecture in the Prefrontal Cortex Leading to Social Impairment and Increased Anxiety

早期生活压力会改变前额叶皮层的基因表达和细胞结构,导致社交障碍和焦虑加剧。

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作者:Noriyoshi Usui ,Yuta Ono ,Ryoko Aramaki ,Stefano Berto ,Genevieve Konopka ,Hideo Matsuzaki ,Shoichi Shimada

Abstract

Early life stress (ELS), such as abuse, neglect, and maltreatment, exhibits a strong impact on the brain and mental development of children. However, it is not fully understood how ELS affects social behaviors and social-associated behaviors as well as developing prefrontal cortex (PFC). In this study, we performed social isolation on weaned pre-adolescent mice until adolescence and investigated these behaviors and PFC characteristics in adolescent mice. We found the ELS induced social impairments in social novelty, social interaction, and social preference in adolescent mice. We also observed increases of anxiety-like behaviors in ELS mice. In histological analysis, we found a reduced number of neurons and an increased number of microglia in the PFC of ELS mice. To identify the gene associated with behavioral and histological features, we analyzed transcriptome in the PFC of ELS mice and identified 15 differentially expressed genes involved in transcriptional regulation, stress, and synaptic signaling. Our study demonstrates that ELS influences social behaviors, anxiety-like behaviors through cytoarchitectural and transcriptomic alterations in the PFC of adolescent mice. Keywords: anxiety; early life stress; prefrontal cortex; social behavior; social isolation; transcriptome.

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