Glutamate receptor subtype expression in human postmortem brain tissue from schizophrenics and alcohol abusers

Area of Science:

• Neuroscience
• Molecular Biology
• Psychiatry

Background:

• Glutamatergic neurotransmission, mediated by AMPA/kainate receptors, is implicated in schizophrenia.
• Previous studies suggest alterations in glutamate receptor subtypes in schizophrenia, but findings are inconsistent.

Purpose of the Study:

• To quantify specific AMPA/kainate (GluR1-3) and kainate (GluR5-7) receptor subtypes in post-mortem human brain tissue from schizophrenic and control subjects.
• To investigate the influence of alcohol abuse history on these receptor levels.

Main Methods:

• Western blotting and densitometry were used to analyze receptor subtype levels in hippocampal and cingulate cortex membrane fractions.
• Antibodies specific to GluR1, GluR2, GluR3, GluR5-7, NCAM, and tau proteins were employed.

Main Results:

• Schizophrenic subjects showed significantly reduced hippocampal GluR2 and GluR3 immunoreactivity compared to all controls.
• Subjects with a history of alcohol abuse exhibited increased hippocampal GluR2 and GluR3 levels.
• When alcohol-abusing subjects were excluded, the difference in GluR2/GluR3 levels between schizophrenic and normal controls was no longer significant.
• No significant changes in GluR1, GluR5, NCAM, or tau were observed in schizophrenia hippocampi.
• Cingulate cortex analysis revealed no group differences in GluR2/GluR3, but smokers had reduced GluR3 levels.

Conclusions:

• Reduced hippocampal GluR2 and GluR3 AMPA/kainate receptor subtypes may be associated with schizophrenia, but this finding is confounded by alcohol abuse.
• Alcohol abuse significantly alters GluR2 and GluR3 levels in the hippocampus.
• These findings highlight the importance of considering alcohol history in schizophrenia neurobiological studies.