The Effects of Chronic Early-life Social Isolation on Hippocampal Cell Number and Hippocampal-Dependent Learning and Memory in Male and Female Rats

Abstract

Before, and for a considerable time after birth, the brain is especially plastic and vulnerable to influences from the environment. Exposure to stressful, or adverse, early-life social experiences, such as social isolation, may impact the brain as it develops and raise susceptibility to developing mental and behavioural disorders. Chronic early-life social isolation (CELSI) is stressful for rats subjected to it, and reproduces a number of behavioural, structural, and neurochemical alterations detected in individuals with schizophrenia. Additionally, the hippocampus, a brain region sensitive to stress, is closely involved in learning and memory and early-life stress has been reported to affect its structure, neuroplasticity, and role in learning and memory. Importantly, few social isolation studies involving rodents have compared both sexes as subjects. Thus, this study explored the impacts of CELSI on brain development and behaviour in adult rats of both sexes. Upon weaning (at postnatal day 21), male and female siblings from 10 Sprague-Dawley rat litters were stratified by sex and randomly assigned to either the group housed (3 animals/cage), or the social isolation (1 animal/cage) condition for 7 weeks. As adults, rats were tested using the Morris Water Maze for 5 days to assess spatial learning and memory. Rats were then sacrificed, and stress-sensitive biometrics, including serum corticosterone levels, were collected. Lastly, the effect of CELSI on neural cell density was investigated by examining the expression of important neuronal and glial proteins (such as PSD-95 and GFAP, respectively) in isolated hippocampal tissue via Western blot analysis. Socially isolated female rats exhibited reduced retroperitoneal fat pads weight and a deficit in acquisition on days 1 and 2 of the acquisition phase. Socially isolated male rats exhibited an enhanced acquisition on day 2 of the acquisition phase and an increased expression of a key neuronal cell marker, PSD-95. As a whole, these data propose a greater negative effect of CELSI on female rats, and, for specific aspects of hippocampal-dependent behaviour, a sexually dimorphic effect of CELSI.