Chronic social defeat stress impairs polysialic acid levels in the hippocampus of mice

OBJECTIVE: Chronic psychological stress is a major cause of various psychiatric disorders, such as depression and anxiety; however, the pathophysiological features of these disorders remain largely unknown. Polysialic acid (PSA), a linear homopolymer of α2-8-linked sialic acid residues, binds to the neural cell adhesion molecule (NCAM) and is involved in cell-to-cell interactions during neural cell migration and neurite outgrowth. Decreased PSA and PSA-NCAM expression have been observed in the brains of patients with psychiatric disorders. Nevertheless, the relationship between psychological stress and PSA has not been clarified. Thus, we examined whether chronic social defeat stress (cSDS), a well-established psychosocial stress model in rodents, affects PSA levels in the male mouse brain. METHODS: Male C57BL/6J mice were exposed to social defeat stress for 10 consecutive days, after which their whole brains were collected. PSA and NCAM protein levels in the hippocampus and prefrontal cortex were analyzed by western blotting. In addition, we measured the expression of genes involved in PSA metabolism by real-time quantitative PCR analysis. RESULTS: Exposure to cSDS decreased PSA and NCAM protein levels in the hippocampus, but not in the prefrontal cortex. We also found that the expression of genes involved in removing sialic acid from NCAM, such as neuraminidase 3 and 4, was significantly elevated in the hippocampus of mice exposed to cSDS. CONCLUSION: We provide evidence showing that psychosocial stress disrupts PSA metabolism in adult mice brains. These findings advance our understanding of the mechanisms underlying the onset of stress-related psychiatric disorders.