Metabotropic glutamate receptor 5 (mGluR5) is involved in hippocampal-dependent learning and memory, which are processes disrupted in
schizophrenia. Recent evidence from human genetic and animal studies suggests that the regulation of mGluR5, including its interaction with trafficking molecules, may be altered in the disorder. However there have been no investigations of hippocampal mGluR5 or mGluR5 trafficking molecules in the postmortem
schizophrenia brain to confirm this. In the present study, we investigated whether
protein expression of mGluR5, as well as
Norbin and Tamalin (modulators of mGluR5 signalling and trafficking), might be altered in the
schizophrenia brain, using postmortem samples from the hippocampal CA1 region of
schizophrenia subjects and matched controls (n=20/group).
Protein levels of mGluR5 (total: 42%, p<0.001; monomer: 25%, p=0.011; dimer: 52%, p<0.001) and mGluR5 trafficking molecules (
Norbin: 47%, p<0.001; Tamalin: 34%, p=0.009) were significantly higher in
schizophrenia subjects compared to controls. To determine any influence of
antipsychotic drug treatment, all
proteins were also correlated with lifetime
chlorpromazine equivalents in patients, and separately measured in the hippocampus of rats exposed to
haloperidol or
olanzapine treatment. mGluR5 was negatively correlated with lifetime
antipsychotic drug exposure in
schizophrenia patients, suggesting
antipsychotic drugs could reduce
mGluR5 protein in
schizophrenia subjects. In contrast, mGluR5 and mGluR5 trafficking molecules were not altered in the hippocampus of
antipsychotic drug treated rats. This investigation provides strong support for the hypothesis that mGluR5 is involved in the pathology of
schizophrenia, and that alterations to mGluR5 trafficking might contribute to the hippocampal-dependent
cognitive dysfunctions associated with this disorder.