Altered dimerization of metabotropic glutamate receptor 3 in schizophrenia.
BACKGROUND
Metabotropic glutamate receptors (mGlus) may be involved in the pathophysiology of schizophrenia. Group II mGlus (mGlu2 and mGlu3) have attracted considerable interest since the development of potent specific agonists that exhibit atypical antipsychotic-like activity and reports of a genetic association between the mGlu3 gene and schizophrenia.


METHODS
In this postmortem study, mGlu3 protein levels in Brodmann area 10 of prefrontal cortex from schizophrenic (n = 20) and control (n = 35) subjects were analyzed by western immunoblotting using a novel specific mGlu3 antibody and an antibody for the vesicular glutamate transporter 1 (VGluT1).


RESULTS
We report a significant decrease in the dimeric/oligomeric forms of mGlu3 in schizophrenic patients compared with control subjects, whereas total mGlu3 and VGluT1 levels were not altered significantly.


CONCLUSIONS
This is the first experimental evidence that mGlu3 receptor levels are altered in schizophrenia and supports the hypothesis that neurotransmission involving this particular excitatory amino acid receptor is impaired in schizophrenia.
Corti
Corrado
C
Department of Biology, Psychiatry Centre of Excellence in Drug Discovery, GlaxoSmithKline Medicines Research Centre, Verona, Italy. corrado.2.corti@gsk.com
Crepaldi
Luca
L
Mion
Silvia
S
Roth
Adelheid L
AL
Xuereb
John H
JH
Ferraguti
Francesco
F
D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D000818:Animals; D000918:Antibody Specificity; D001344:Autopsy; D015153:Blotting, Western; D015331:Cohort Studies; D003720:Densitometry; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008875:Middle Aged; D008969:Molecular Sequence Data; D018094:Receptors, Metabotropic Glutamate / Q000235:genetics* / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D012559:Schizophrenia / Q000235:genetics* / Q000378:metabolism*
D018094:Receptors, Metabotropic Glutamate; D011994:Recombinant Proteins; C108822:metabotropic glutamate receptor 2; C102718:metabotropic glutamate receptor 3