Glycosylation enzyme mRNA expression in dorsolateral prefrontal cortex of elderly patients with schizophrenia: Evidence for dysregulation of multiple glycosylation pathways

Abstract

Altered protein post-translational modifications such as glycosylation have become a target of investigation in the pathophysiology of schizophrenia. Disrupted glycosylation associated processes including atypical sphingolipid metabolism, reduced polysialylation of cell adhesion molecules, abnormal proteoglycan expression, and irregular glycan synthesis and branching have also been reported in this disorder. These pathways are regulated by the expression of glycosidases and glycosyltransferases, classes of enzymes which comprise approximately 2% of the genome. Many glycosylation enzymes can participate in multiple glycosylation pathways and dysregulation of enzyme expression could represent a common mechanism leading to a variety of glycan processing deficits in schizophrenia. In matched pairs of elderly schizophrenia and comparison subject (N = 12 pairs) dorsolateral prefrontal cortex, we measured mRNA levels of 84 key glycosylation enzymes by qPCR array. We found dysregulated transcript expression of 36 glycosylation enzymes from 12 functional categories. All of the abnormally expressed enzymes demonstrated increased transcript expression in schizophrenia, and many altered enzymes are known to modify substrates that have been previously implicated in the pathophysiology this illness. These findings suggest that abnormal glycosylation enzyme expression in schizophrenia may contribute to dysregulation of multiple glycosylation pathways, and disruptions of these central cell signaling processes may underlie a variety of deficits in schizophrenia.