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Hippocampal Neurogenesis, Cognitive Deficits and Affective Disorder in Huntington's Disease
Huntington's disease (HD) is a neurodegenerative disorder caused by a tandem repeat expansion encoding a polyglutamine tract in the huntingtin protein. HD involves progressive psychiatric, cognitive, and motor symptoms, the selective pathogenesis of which remains to be mechanistically elucidate...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi Publishing Corporation
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3394391/ https://www.ncbi.nlm.nih.gov/pubmed/22830053 http://dx.doi.org/10.1155/2012/874387 |
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author | Ransome, Mark I. Renoir, Thibault Hannan, Anthony J. |
author_facet | Ransome, Mark I. Renoir, Thibault Hannan, Anthony J. |
author_sort | Ransome, Mark I. |
collection | PubMed |
description | Huntington's disease (HD) is a neurodegenerative disorder caused by a tandem repeat expansion encoding a polyglutamine tract in the huntingtin protein. HD involves progressive psychiatric, cognitive, and motor symptoms, the selective pathogenesis of which remains to be mechanistically elucidated. There are a range of different brain regions, including the cerebral cortex and striatum, known to be affected in HD, with evidence for hippocampal dysfunction accumulating in recent years. In this review we will focus on hippocampal abnormalities, in particular, deficits of adult neurogenesis. We will discuss potential molecular mechanisms mediating disrupted hippocampal neurogenesis, and how this deficit of cellular plasticity may in turn contribute to specific cognitive and affective symptoms that are prominent in HD. The generation of transgenic animal models of HD has greatly facilitated our understanding of disease mechanisms at molecular, cellular, and systems levels. Transgenic HD mice have been found to show progressive behavioral changes, including affective, cognitive, and motor abnormalities. The discovery, in multiple transgenic lines of HD mice, that adult hippocampal neurogenesis and synaptic plasticity is disrupted, may help explain specific aspects of cognitive and affective dysfunction. Furthermore, these mouse models have provided insight into potential molecular mediators of adult neurogenesis deficits, such as disrupted serotonergic and neurotrophin signaling. Finally, a number of environmental and pharmacological interventions which are known to enhance adult hippocampal neurogenesis have been found to have beneficial affective and cognitive effects in mouse models, suggesting common molecular targets which may have therapeutic utility for HD and related diseases. |
format | Online Article Text |
id | pubmed-3394391 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Hindawi Publishing Corporation |
record_format | MEDLINE/PubMed |
spelling | pubmed-33943912012-07-24 Hippocampal Neurogenesis, Cognitive Deficits and Affective Disorder in Huntington's Disease Ransome, Mark I. Renoir, Thibault Hannan, Anthony J. Neural Plast Review Article Huntington's disease (HD) is a neurodegenerative disorder caused by a tandem repeat expansion encoding a polyglutamine tract in the huntingtin protein. HD involves progressive psychiatric, cognitive, and motor symptoms, the selective pathogenesis of which remains to be mechanistically elucidated. There are a range of different brain regions, including the cerebral cortex and striatum, known to be affected in HD, with evidence for hippocampal dysfunction accumulating in recent years. In this review we will focus on hippocampal abnormalities, in particular, deficits of adult neurogenesis. We will discuss potential molecular mechanisms mediating disrupted hippocampal neurogenesis, and how this deficit of cellular plasticity may in turn contribute to specific cognitive and affective symptoms that are prominent in HD. The generation of transgenic animal models of HD has greatly facilitated our understanding of disease mechanisms at molecular, cellular, and systems levels. Transgenic HD mice have been found to show progressive behavioral changes, including affective, cognitive, and motor abnormalities. The discovery, in multiple transgenic lines of HD mice, that adult hippocampal neurogenesis and synaptic plasticity is disrupted, may help explain specific aspects of cognitive and affective dysfunction. Furthermore, these mouse models have provided insight into potential molecular mediators of adult neurogenesis deficits, such as disrupted serotonergic and neurotrophin signaling. Finally, a number of environmental and pharmacological interventions which are known to enhance adult hippocampal neurogenesis have been found to have beneficial affective and cognitive effects in mouse models, suggesting common molecular targets which may have therapeutic utility for HD and related diseases. Hindawi Publishing Corporation 2012 2012-06-27 /pmc/articles/PMC3394391/ /pubmed/22830053 http://dx.doi.org/10.1155/2012/874387 Text en Copyright © 2012 Mark I. Ransome et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Review Article Ransome, Mark I. Renoir, Thibault Hannan, Anthony J. Hippocampal Neurogenesis, Cognitive Deficits and Affective Disorder in Huntington's Disease |
title | Hippocampal Neurogenesis, Cognitive Deficits and Affective Disorder in Huntington's Disease |
title_full | Hippocampal Neurogenesis, Cognitive Deficits and Affective Disorder in Huntington's Disease |
title_fullStr | Hippocampal Neurogenesis, Cognitive Deficits and Affective Disorder in Huntington's Disease |
title_full_unstemmed | Hippocampal Neurogenesis, Cognitive Deficits and Affective Disorder in Huntington's Disease |
title_short | Hippocampal Neurogenesis, Cognitive Deficits and Affective Disorder in Huntington's Disease |
title_sort | hippocampal neurogenesis, cognitive deficits and affective disorder in huntington's disease |
topic | Review Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3394391/ https://www.ncbi.nlm.nih.gov/pubmed/22830053 http://dx.doi.org/10.1155/2012/874387 |
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