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Metabotropic glutamate receptor 5 binding and protein expression in schizophrenia and following antipsychotic drug treatment

journal contribution
posted on 2024-11-16, 07:44 authored by Natalie MatosinNatalie Matosin, Elisabeth Frank, Chao DengChao Deng, Xu-Feng HuangXu-Feng Huang, Kelly NewellKelly Newell
Metabotropic glutamate receptor 5 (mGluR5) has been identified as a potential therapeutic target for schizophrenia, primarily due to its ability to indirectly modulate glutamatergic signalling through the NMDA receptor (NMDAR). Despite its potential, molecular studies characterising mGluR5 in schizophrenia are limited. We therefore aimed to determine if the mGluR5 binding site or protein levels were altered in schizophrenia or by current antipsychotics. Using in-situ radioligand binding and immunoblot, we measured [3H]MPEP binding to mGluR5 and mGluR5 protein density in the post-mortem dorsolateral prefrontal cortex (DLPFC; BA46) of 37 schizophrenia and 37 matched control subjects. Subsequently, we measured [3H]MPEP binding in rat brains following typical (haloperidol) or atypical (olanzapine) antipsychotic treatment (n = 6/group). Subjects with schizophrenia showed no significant alteration in mGluR5 binding density or mGluR5 protein levels. Furthermore, mGluR5 binding in the rat cortex, thalamus, hippocampus and striatum was unaltered by short-, medium- and long-term antipsychotic treatment. Our data suggests that there are no alterations in mGluR5 in schizophrenia subjects. The lack of alteration in mGluR5 binding and protein in schizophrenia is advantageous because its ability to modulate the NMDAR is potentially unhindered, thereby supporting the development of novel antipsychotic agents that work through the mGluR5/NMDAR complex.

Funding

Temporal trends, spatial distribution, migration flows and factors associated with leprosy in the state of Piauí and in the five neighboring states, 2006-2017

Coordenação de Aperfeicoamento de Pessoal de Nível Superior

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Citation

Matosin, N., Frank, E., Deng, C., Huang, X. & Newell, K. A. 2013, 'Metabotropic glutamate receptor 5 binding and protein expression in schizophrenia and following antipsychotic drug treatment', Schizophrenia Research, vol. 146, no. 1-3, pp. 170-176.

Journal title

Schizophrenia Research

Volume

146

Issue

1/03/2024

Pagination

170-176

Language

English

RIS ID

77454

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