chondroitin-sulfates and Schizophrenia

Perineuronal nets comprise chondroitin sulfate moieties and their core proteins, and their neuropathological alterations have been implicated in schizophrenia. To explore the molecular mechanism of the perineuronal net impairments in schizophrenia, we measured the immunoreactivity of chondroitin sulfate moieties, major components of perineuronal nets, in three brain regions (postmortem dorsolateral prefrontal cortex, caudate nucleus, and hippocampus) of schizophrenia patients and control subjects. Immunoblotting for chondroitin 4-sulfate and chondroitin 6-sulfate moieties revealed a significant increase in intensity of a 180 kD band of chondroitin 4-sulfate immunoreactivity in the hippocampus of patients, although we detected no significant alteration in their immunoreactivities with any other molecular sizes or in other brain regions. The levels of immunoreactivity were not correlated with postmortem interval, age, or storage time. We failed to find such an increase in a similar molecular range of the chondroitin 4-sulfate immunoreactivity in the hippocampus of the rats chronically treated with haloperidol. These results suggest that the level alteration of the chondroitin 4-sulfate moiety might contribute to the perineuronal net abnormality found in patients with schizophrenia.

Topics: Aged; Animals; Case-Control Studies; Caudate Nucleus; Chondroitin Sulfates; Extracellular Matrix; Female; Hippocampus; Humans; Male; Middle Aged; Prefrontal Cortex; Rats; Schizophrenia

Perineuronal nets (PNNs) are specialized extracellular matrix aggregates surrounding distinct neuronal populations and regulating synaptic functions and plasticity. Previous findings showed robust PNN decreases in amygdala, entorhinal cortex and prefrontal cortex of subjects with schizophrenia (SZ), but not bipolar disorder (BD). These studies were carried out using a chondroitin sulfate proteoglycan (CSPG) lectin marker. Here, we tested the hypothesis that the CSPG aggrecan, and 6-sulfated chondroitin sulfate (CS-6) chains highly represented in aggrecan, may contribute to these abnormalities. Antibodies against aggrecan and CS-6 (3B3 and CS56) were used in the amygdala of healthy control, SZ and BD subjects. In controls, aggrecan immunoreactivity (IR) was observed in PNNs and glial cells. Antibody 3B3, but not CS56, also labeled PNNs in the amygdala. In addition, dense clusters of CS56 and 3B3 IR encompassed CS56- and 3B3-IR glia, respectively. In SZ, numbers of aggrecan- and 3B3-IR PNNs were decreased, together with marked reductions of aggrecan-IR glial cells and CS-6 (3B3 and CS56)-IR 'clusters'. In BD, numbers of 3B3-IR PNNs and CS56-IR clusters were reduced. Our findings show disruption of multiple PNN populations in the amygdala of SZ and, more modestly, BD. Decreases of aggrecan-IR glia and CS-6-IR glial 'clusters', in sharp contrast to increases of CSPG/lectin-positive glia previously observed, indicate that CSPG abnormalities may affect distinct glial cell populations and suggest a potential mechanism for PNN decreases. Together, these abnormalities may contribute to a destabilization of synaptic connectivity and regulation of neuronal functions in the amygdala of subjects with major psychoses.

Topics: Adult; Aged; Aged, 80 and over; Aggrecans; Amygdala; Bipolar Disorder; Case-Control Studies; Chondroitin Sulfates; Female; Humans; Immunohistochemistry; Male; Middle Aged; Neuroglia; Schizophrenia

A reliable and reproducible method for the simultaneous determination of neutral sugars and hexosamines in glycoproteins and acid mucopolysaccharides has been described. It involves the following steps: the release of neutral sugars and hexosamines from biopolymers by resin-catalysed hydrolysis, the nitrous acid deamination of resin-bound hexosamines in this hydrolysate to aldoses, and the determination of these newly formed anhydroaldoses together with the pre-existing neutral sugars as aldononitrile acetates by gas chromatography. Applications of this method to analyses of glycoprotein from urine of schizophrenic patients, bovine thyroglobulin, human brain glycoprotein, chondroitin sulfates from bovine vitreous humor, and veal brain, and human umbilical cord hyaluronic acid are given.

Topics: Animals; Brain Chemistry; Cattle; Chondroitin Sulfates; Chromatography, Gas; Chromatography, Liquid; Glycoproteins; Glycosaminoglycans; Hexosamines; Hexoses; Humans; Hyaluronic Acid; Methods; Schizophrenia; Umbilical Cord; Vitreous Body