Comparative Studies of Glutamine Synthetase Levels in the Brains of Patients with Schizophrenia and Mentally Healthy People

Abstract

In this study the authors compared the levels of glutamine synthetase (GS) enzymatic activities, as well as the levels of immunoreactive GS and GS-like protein (GSLP) in the readily soluble protein fraction of brain samples taken during autopsies of patients with schizophrenia and subjects from a control group. Enzymatic GS activity was measured and levels of immunoreactive GS and GSLP were determined in postmortem samples of the prefrontal, anterior, and posterior cingulate cortex (Brodmann areas 10, 24, and 23, respectively) and cerebellum cortex obtained from patients with schizophrenia (n = 8) and a control group (n = 9), matched according to age and postmortem interval. GS activity was evaluated in vitro in the “transferase” reaction by the formation of γ-glutamyl hydroxamate, and the levels of immunoreactive GS and GSLP were evaluated by ECL Western blotting using monoclonal and polyclonal antibodies. No differences in GS enzymatic activity were found in all of the studied brain structures. The level of immunoreactive GS in the prefrontal cortex was significantly decreased in patients with schizophrenia compared with the controls (at p < 0.001 according to the Mann–Whitney U-test); it was unchanged in the posterior cingulate cortex and significantly elevated in the anterior cingulate cortex and cerebellum (p < 0.001 and p < 0.004, respectively), whereas the level of immunoreactive GSLP was elevated in all studied brain areas (p < 0.004, p < 0.02, p < 0.04, and p < 0.006, respectively). The alteration of GS and GSLP levels in brains of patients with schizophrenia is one of the factors that disturb glutamate metabolism in these brain structures and is an important aspect of schizophrenia pathogenesis.