Effect of olanzapine treatment on platelet glutamine synthetase-like protein and glutamate dehydrogenase immunoreactivity in schizophrenia

Abstract

According to contemporary views, the glutamatergic system is implicated in the pathogenesis of schizophrenia, and atypical neuroleptics exert their effects (at least partially) through the glutamatergic system. Immunoreactive glutamate-metabolising enzymes, such as glutamine synthetase-like protein (GSLP) and two glutamate dehydrogenase isoenzymes (GDH), have been discovered in human platelets. The amount of GSLP in the platelets of 40 chronic patients with schizophrenia was found to be significantly higher than in 33 controls (consistent with our previous finding of increased amounts of GSLP in the prefrontal cortex of chronic schizophrenia patients). Moreover, survival analysis of the group of patients treated with olanzapine for 28 weeks showed that the larger amount of GSLP measured in platelets before treatment, the shorter the treatment time needed to achieve a positive clinical response (defined a priori as > or = 20% reduction in PANSS total score from the initial level before the treatment). Hence, GSLP level may serve as a predictor of the treatment duration to achieve a positive outcome with olanzapine. Both GSLP and GDH were found significantly changed in the course of treatment; hence, treatment with olanzapine influences the amounts of glutamate-metabolising enzymes in the platelets of chronic schizophrenia patients.

Neuroprogression in schizophrenia: Pathways underpinning clinical staging and therapeutic corollaries

“…Transcription studies have demonstrated alterations in proteins involved in the binding and transmission of glutamate within the thalamus, including those which interact with the NMDA receptor (Bruneau et al, 2005). Proteins for the degradation and transport of breakdown products of glutamate have also been suggested to be up-regulated within the thalamus, including glutamine synthase (GS), vesicular glutamate transporter (VGLUT), phosphoprotein associated with glycosphingolipidenriched microdomains (PAG), excitatory amino-acid transporters (EAAT) 1 and 2 (Bruneau et al, 2005), glutamine-synthase-like protein (GSLP) and glutamate dehydrogenase (GDH) (Burbaeva et al, 2006). Glutamine, the breakdown product of glutamate, has been shown to be increased within the thalamus in both antipsychotic naïve and chronically medicated patients (Theberge et al, 2003).…”

Cortical expression of glial fibrillary acidic protein and glutamine synthetase is decreased in schizophrenia

“…Studies measuring glutamine synthetase protein levels in the brain do not find changes that can be related to antipsychotic treatment (Burbaeva et al, 2003, Toro et al, 2006. However, recently it was reported that peripheral protein levels of GSLP, an isoform of glutamine synthetase, may be altered by treatment with antipsychotics (Burbaeva et al, 2006). Burbaeva and colleagues demonstrated that increased platelet expression of GSLP in schizophrenia is reduced following treatment with the atypical antipsychotic, olanzapine.…”

Platelet cytochrome c-oxidase activity in patients with acute schizophrenia in the course of their treatment with risperidone

“…So, our special attention was paid to the treatment efficiency (clinical response) evaluation in the patients. In our previous study, when searching for biochemical predictor of pharmacological therapy efficiency we have taken the decrease in PANSS total for positive treatment effect [26]. In the present work, we additionally regard PANSS positive, PANSS negative, PANSS psychopathological, NSA, and neurocognitive tests.…”