Schizophrenia, bipolar disorder, autism spectrum disorder, and major depression are common mental disorders. To understand and treat these pathologies, it is important to focus on the pathogen-associated molecular patterns that are predominant in the brain and are specifically altered in mental disorders. The polysialic acid (polySia/PSA) chain, which specifically modifies the neuronal cell adhesion molecule (NCAM) protein (Figure 1), is aberrantly expressed in mental disorders1-3). So far, the relationship between the polySia chain and mental disorders was studied by performing and pioneering various biochemical analyses of disease-associated SNPs of the polySia synthase ST8SIA2 gene, and it was found that all the disease-associated SNPs resulted in the structural and functional impairments of polySia1-3). As it is important to consider both the genetic and environmental factors to ascertain the etiology of mental disorders, exploring the effects of environmental factors on polySia expression in the brain was focused on. The tail Figure 1. NCAM and polysialylated NCAMOn the left: the structure of neural cell adhesion molecule (NCAM). NCAM consists of five Ig domains, two FN type III domains, transmembrane domains, and cytosolic regions. NCAM exhibits homophilic and heterophilic reactions. Polysialylated NCAM is the NCAM having polysialylated N-glycans on the Ig5 domain. Polysialic acid (polySia) in the brain is the 2,8-linked polyNeu5Ac, and it has helical or random structures. It has large exclusion volume; therefore, polySia-NCAM exhibits anti-adhesive effects on molecules and membranes.20211).suspension test that predisposes mice to an acute stress as a negative environmental factor was adopted. Immunochemical and chemical analyses were conducted to ascertain the polySia expression levels in the following five brain regions: olfactory bulb (OB), prefrontal cortex (PFC), amygdala (AMG), suprachiasmatic nucleus (SCN), and hippocampus (HIP). Finally, it was found that a 7-min acute stress led to alteration of the polySia expression levels in the specified brain regions. We observed a decrease in the polySia expression levels in the OB and PFC, and the underlying mechanism for this decrease by acute stress was attributed to sialidase from microglia or astrocyte4). Therefore, it is clearly demonstrated that apart from genetics, environmental factors also affect polySia expression in specific brain and expression level of polySia is highly regulated by both genetic and environmental factors. Methods and ResultsAcute stress as an environmental factor: Mice (C57/BL6J, male, 10–12 weeks) were maintained in a controlled environment (23 ± 2 °C and 50 ± 10 % humidity, 12h light/dark cycle), with food and water available ad libitum. The mice were acclimated to our facilities at least 1 week prior to the experiments; they were kept in the experimental room for an hour to habituate them to the environment. Subsequent to habituation, the mice were suspended over 30 cm above the floor; they were maintained in this suspended state by their tails for 7 min (tail suspension, TS). Subsequent to TS, the blood and brain samples were collected for analysis. The concentration of corticosterone and the polySia expression levels in the five brain regions were analyzed via immunostaining with two different types of anti-polySia antibodies3,5) and using chemical analyses3,6). Following TS, an increased concentration of the serum corticosterone was observed, which showed that TS induced an acute stress in the mice. Moreover, the polySia 60Effects of environmental factors on the quantity and quality of polysialic acid in the brainChihiro SatoBioscience and Biotechnology Center, Department of Bioagricultural Sciences,Institute for Glyco-Core Research, Nagoya University
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