Background:Although polySia is known to retain neurotrophins, their releasing mechanism remains unknown. Results: PolySia present on the cell surface of microglia is rapidly cleared by Neu1 sialidase on exovesicles secreted upon inflammatory stimulus, leading to neurotrophin release. Conclusion: Exovesicular Neu1 regulates rapid turnover of polySia and concomitant neurotrophin function. Significance: First demonstration of on-site turnover of polySia and its physiological significance.

A number of loci are associated with highly heritable schizophrenia and the prevalence of this mental illness has had considerable negative fitness effects on human populations. Here we focused on one particular schizophrenia-associated gene that encodes a sialyltransferase (ST8SIA2) and is expressed preferentially in the brain with the level being largely determined by three SNPs in the promoter region. It is suggested that the expression level of the ST8SIA2 gene is a genetic determinant of schizophrenia risk, and we found that a geographically differentiated non-risk SNP type (-type) has significantly reduced promoter activity. A newly developed method for detecting ongoing positive selection was applied to the ST8SIA2 genomic region with the identification of an unambiguous sweep signal in a rather restricted region of 18 kb length surrounding the promoter. We also found that while the -type emerged in anatomically modern humans in Africa over 100 thousand years ago, it has increased its frequency in Asia only during the past 20–30 thousand years. These findings support that the positive selection is driven by psychosocial stress due to changing social environments since around the last glacial maximum, and raise a possibility that schizophrenia extensively emerged during the Upper Paleolithic and Neolithic era.

Background: Polysialic acid (polySia) binds neurological factors, BDNF and dopamine. Results: PolySia specifically binds FGF2 and inhibits the cell growth facilitated by signaling through a ternary complex of FGF2, FGFR, and heparan sulfate (HS). Conclusion: PolySia regulates the FGF2-mediated cell growth differently from HS. Significance: A new function of polySia to regulate the action of neurological factors is established.

Background: Anti-polysialic acid monoclonal antibody mAb735 preferentially binds longer polysialic acid chains. Results: Crystal structure of the single chain Fv fragment was determined in complex with octasialic acid. Conclusion: Two linked units of three consecutive sialic acid residues interact with two antibody fragments in extended conformation. Significance: An immunological strategy for preference of longer polysialic acid polymers is revealed conflicting with the conformational epitope hypothesis.