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Metabotropic glutamate receptor 5, and its trafficking molecules Norbin and Tamalin, are increased in the CA1 hippocampal region of subjects with schizophrenia
Matosin, Natalie Fernandez-Enright, Francesca Elizabeth Lum, Jeremy S. Andrews, Jessica L. Engel, Martin Huang, Xu-Feng Newell, Kelly A.
Matosin, Natalie
Fernandez-Enright, Francesca Elizabeth
Lum, Jeremy S.
Andrews, Jessica L.
Engel, Martin
Huang, Xu-Feng
Newell, Kelly A.
Abstract
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.
Keywords
mGluR5, hippocampus, norbin, tamalin, trafficking, schizophrenia
Date
2015
Type
Journal article
Journal
Schizophrenia Research
Book
Volume
166
Issue
2017-03-01
Page Range
212-218
Article Number
ACU Department
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Open Access Status
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Controlled