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The role of the cerebellum in schizophrenia: from cognition to molecular pathways

Beside its role in motor coordination, the cerebellum is involved in cognitive function such as attention, working memory, verbal learning, and sensory discrimination. In schizophrenia, a disturbed prefronto-thalamo-cerebellar circuit has been proposed to play a role in the pathophysiology. In addit...

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Autores principales: Yeganeh-Doost, Peyman, Gruber, Oliver, Falkai, Peter, Schmitt, Andrea
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3118440/
https://www.ncbi.nlm.nih.gov/pubmed/21779725
http://dx.doi.org/10.1590/S1807-59322011001300009
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author Yeganeh-Doost, Peyman
Gruber, Oliver
Falkai, Peter
Schmitt, Andrea
author_facet Yeganeh-Doost, Peyman
Gruber, Oliver
Falkai, Peter
Schmitt, Andrea
author_sort Yeganeh-Doost, Peyman
collection PubMed
description Beside its role in motor coordination, the cerebellum is involved in cognitive function such as attention, working memory, verbal learning, and sensory discrimination. In schizophrenia, a disturbed prefronto-thalamo-cerebellar circuit has been proposed to play a role in the pathophysiology. In addition, a deficit in the glutamatergic N-methyl-D-aspartate (NMDA) receptor has been hypothesized. The risk gene neuregulin 1 may play a major role in this process. We demonstrated a higher expression of the NMDA receptor subunit 2D in the right cerebellar regions of schizophrenia patients, which may be a secondary upregulation due to a dysfunctional receptor. In contrast, the neuregulin 1 risk variant containing at least one C-allele was associated with decreased expression of NMDA receptor subunit 2C, leading to a dysfunction of the NMDA receptor, which in turn may lead to a dysfunction of the gamma amino butyric acid (GABA) system. Accordingly, from post-mortem studies, there is accumulating evidence that GABAergic signaling is decreased in the cerebellum of schizophrenia patients. As patients in these studies are treated with antipsychotics long term, we evaluated the effect of long-term haloperidol and clozapine treatment in an animal model. We showed that clozapine may be superior to haloperidol in restoring a deficit in NMDA receptor subunit 2C expression in the cerebellum. We discuss the molecular findings in the light of the role of the cerebellum in attention and cognitive deficits in schizophrenia.
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spelling pubmed-31184402011-06-22 The role of the cerebellum in schizophrenia: from cognition to molecular pathways Yeganeh-Doost, Peyman Gruber, Oliver Falkai, Peter Schmitt, Andrea Clinics (Sao Paulo) Editorial Beside its role in motor coordination, the cerebellum is involved in cognitive function such as attention, working memory, verbal learning, and sensory discrimination. In schizophrenia, a disturbed prefronto-thalamo-cerebellar circuit has been proposed to play a role in the pathophysiology. In addition, a deficit in the glutamatergic N-methyl-D-aspartate (NMDA) receptor has been hypothesized. The risk gene neuregulin 1 may play a major role in this process. We demonstrated a higher expression of the NMDA receptor subunit 2D in the right cerebellar regions of schizophrenia patients, which may be a secondary upregulation due to a dysfunctional receptor. In contrast, the neuregulin 1 risk variant containing at least one C-allele was associated with decreased expression of NMDA receptor subunit 2C, leading to a dysfunction of the NMDA receptor, which in turn may lead to a dysfunction of the gamma amino butyric acid (GABA) system. Accordingly, from post-mortem studies, there is accumulating evidence that GABAergic signaling is decreased in the cerebellum of schizophrenia patients. As patients in these studies are treated with antipsychotics long term, we evaluated the effect of long-term haloperidol and clozapine treatment in an animal model. We showed that clozapine may be superior to haloperidol in restoring a deficit in NMDA receptor subunit 2C expression in the cerebellum. We discuss the molecular findings in the light of the role of the cerebellum in attention and cognitive deficits in schizophrenia. Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo 2011-06 /pmc/articles/PMC3118440/ /pubmed/21779725 http://dx.doi.org/10.1590/S1807-59322011001300009 Text en Copyright © 2011 Hospital das Clínicas da FMUSP http://creativecommons.org/licenses/by-nc/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Editorial
Yeganeh-Doost, Peyman
Gruber, Oliver
Falkai, Peter
Schmitt, Andrea
The role of the cerebellum in schizophrenia: from cognition to molecular pathways
title The role of the cerebellum in schizophrenia: from cognition to molecular pathways
title_full The role of the cerebellum in schizophrenia: from cognition to molecular pathways
title_fullStr The role of the cerebellum in schizophrenia: from cognition to molecular pathways
title_full_unstemmed The role of the cerebellum in schizophrenia: from cognition to molecular pathways
title_short The role of the cerebellum in schizophrenia: from cognition to molecular pathways
title_sort role of the cerebellum in schizophrenia: from cognition to molecular pathways
topic Editorial
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3118440/
https://www.ncbi.nlm.nih.gov/pubmed/21779725
http://dx.doi.org/10.1590/S1807-59322011001300009
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