mGluR5 + its trafficking molecules are increased in the hippocampus in schizophrenia
Metabotropic glutamate receptor 5, and its trafficking molecules Norbin and Tamalin, are increased in the CA1 hippocampal region of subjects with schizophrenia
Matosin N, Fernandez-Enright F, Lum JS, Andrews JL, Engel M, Huang XF, Newell KA. Metabotropic glutamate receptor 5 and its trafficking molecules, Norbin and Tamalin, are increased in the CA1 hippocampal region of subjects with schizophrenia. In press, Schizophrenia Research. 2015.
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.
Click here to access a pre-print copy.
natalie matosin | blog 
[…] Another reason that postmortem studies can sometimes be deprecated is because they are “descriptive and correlational [1]”, as opposed to in vivo and in vitro studies where the systems can be manipulated, and then the consequences of this manipulation observed in other ways, like rebound chemical reactions and molecular changes, or changes to animal behaviour. In postmortem human studies, you can measure molecules of interest, but you can’t manipulate them. There are of course still ways that we can gain circumstantial information about active processes that might have been occurring within the brain – for example, in our recent articles we measured molecules with known functions as markers of receptor signalling and trafficking. […]
LikeLike