Long-term social isolation in the adulthood results in CA1 shrinkage and cognitive impairment

•Hippocampal CA1 subregion is essential to contextual memory.•Social isolation impairs contextual fear conditioning.•Social isolation results with CA11 shrinkage and decreased synaptic PSA-NCAM. Social isolation in adulthood is a psychosocial stressor that can result in endocrinological and behavioral alterations in different species. In rodents, controversial results have been obtained in fear conditioning after social isolation at adulthood, while neural substrates underlying these differences are largely unknown. Neural cell adhesion molecule (NCAM) and its polysialylated form (PSA-NCAM) are prominent modulators of synaptic plasticity underlying memory processes in many tasks, including fear conditioning. In this study, we used adult female Octodon degus to investigate the effects of long-term social isolation on contextual and cued fear conditioning, and the possible modulation of the synaptic levels of NCAM and PSA-NCAM in the hippocampus. After 6½months of social isolation, adult female degus showed a normal auditory-cued fear memory, but a deficit in contextual fear memory, a hippocampal dependent task. Subsequently, we observed reduced hippocampal synaptic levels of PSA-NCAM in isolated compared to grouped-housed female degus. No significant differences were found between experimental groups in hippocampal levels of the three main isoforms of NCAM (NCAM180, NCAM140 and NCAM120). Interestingly, social isolation reduced the volume of the hippocampal CA1 subfield, without affecting the volume of the CA3 subregion or the total hippocampus. Moreover, attenuated body weight gain and reduced number of granulocytes were detected in isolated animals. Our findings indicate for the first time, that long-term social isolation of adult female animals induces a specific shrinkage of CA1 and a decrease in synaptic levels of PSA-NCAM in the hippocampus. These effects may be related to the deficit in contextual fear memory observed in isolated female degus.