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Reduction in Subventricular Zone-Derived Olfactory Bulb Neurogenesis in a Rat Model of Huntington’s Disease Is Accompanied by Striatal Invasion of Neuroblasts

Huntington’s disease (HD) is an inherited progressive neurodegenerative disorder caused by an expanded CAG repeat in exon 1 of the huntingtin gene (HTT). The primary neuropathology of HD has been attributed to the preferential degeneration of medium spiny neurons (MSN) in the striatum. Reports on st...

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Autores principales: Kandasamy, Mahesh, Rosskopf, Michael, Wagner, Katrin, Klein, Barbara, Couillard-Despres, Sebastien, Reitsamer, Herbert A., Stephan, Michael, Nguyen, Huu Phuc, Riess, Olaf, Bogdahn, Ulrich, Winkler, Jürgen, von Hörsten, Stephan, Aigner, Ludwig
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4342015/
https://www.ncbi.nlm.nih.gov/pubmed/25719447
http://dx.doi.org/10.1371/journal.pone.0116069
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author Kandasamy, Mahesh
Rosskopf, Michael
Wagner, Katrin
Klein, Barbara
Couillard-Despres, Sebastien
Reitsamer, Herbert A.
Stephan, Michael
Nguyen, Huu Phuc
Riess, Olaf
Bogdahn, Ulrich
Winkler, Jürgen
von Hörsten, Stephan
Aigner, Ludwig
author_facet Kandasamy, Mahesh
Rosskopf, Michael
Wagner, Katrin
Klein, Barbara
Couillard-Despres, Sebastien
Reitsamer, Herbert A.
Stephan, Michael
Nguyen, Huu Phuc
Riess, Olaf
Bogdahn, Ulrich
Winkler, Jürgen
von Hörsten, Stephan
Aigner, Ludwig
author_sort Kandasamy, Mahesh
collection PubMed
description Huntington’s disease (HD) is an inherited progressive neurodegenerative disorder caused by an expanded CAG repeat in exon 1 of the huntingtin gene (HTT). The primary neuropathology of HD has been attributed to the preferential degeneration of medium spiny neurons (MSN) in the striatum. Reports on striatal neurogenesis have been a subject of debate; nevertheless, it should be considered as an endogenous attempt to repair the brain. The subventricular zone (SVZ) might offer a close-by region to supply the degenerated striatum with new cells. Previously, we have demonstrated that R6/2 mice, a widely used preclinical model representing an early onset HD, showed reduced olfactory bulb (OB) neurogenesis but induced striatal migration of neuroblasts without affecting the proliferation of neural progenitor cell (NPCs) in the SVZ. The present study revisits these findings, using a clinically more relevant transgenic rat model of late onset HD (tgHD rats) carrying the human HTT gene with 51 CAG repeats and mimicking many of the neuropathological features of HD seen in patients. We demonstrate that cell proliferation is reduced in the SVZ and OB of tgHD rats compared to WT rats. In the OB of tgHD rats, although cell survival was reduced, the frequency of neuronal differentiation was not altered in the granule cell layer (GCL) compared to the WT rats. However, an increased frequency of dopamenergic neuronal differentiation was noticed in the glomerular layer (GLOM) of tgHD rats. Besides this, we observed a selective proliferation of neuroblasts in the adjacent striatum of tgHD rats. There was no evidence for neuronal maturation and survival of these striatal neuroblasts. Therefore, the functional role of these invading neuroblasts still needs to be determined, but they might offer an endogenous alternative for stem or neuronal cell transplantation strategies.
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spelling pubmed-43420152015-03-04 Reduction in Subventricular Zone-Derived Olfactory Bulb Neurogenesis in a Rat Model of Huntington’s Disease Is Accompanied by Striatal Invasion of Neuroblasts Kandasamy, Mahesh Rosskopf, Michael Wagner, Katrin Klein, Barbara Couillard-Despres, Sebastien Reitsamer, Herbert A. Stephan, Michael Nguyen, Huu Phuc Riess, Olaf Bogdahn, Ulrich Winkler, Jürgen von Hörsten, Stephan Aigner, Ludwig PLoS One Research Article Huntington’s disease (HD) is an inherited progressive neurodegenerative disorder caused by an expanded CAG repeat in exon 1 of the huntingtin gene (HTT). The primary neuropathology of HD has been attributed to the preferential degeneration of medium spiny neurons (MSN) in the striatum. Reports on striatal neurogenesis have been a subject of debate; nevertheless, it should be considered as an endogenous attempt to repair the brain. The subventricular zone (SVZ) might offer a close-by region to supply the degenerated striatum with new cells. Previously, we have demonstrated that R6/2 mice, a widely used preclinical model representing an early onset HD, showed reduced olfactory bulb (OB) neurogenesis but induced striatal migration of neuroblasts without affecting the proliferation of neural progenitor cell (NPCs) in the SVZ. The present study revisits these findings, using a clinically more relevant transgenic rat model of late onset HD (tgHD rats) carrying the human HTT gene with 51 CAG repeats and mimicking many of the neuropathological features of HD seen in patients. We demonstrate that cell proliferation is reduced in the SVZ and OB of tgHD rats compared to WT rats. In the OB of tgHD rats, although cell survival was reduced, the frequency of neuronal differentiation was not altered in the granule cell layer (GCL) compared to the WT rats. However, an increased frequency of dopamenergic neuronal differentiation was noticed in the glomerular layer (GLOM) of tgHD rats. Besides this, we observed a selective proliferation of neuroblasts in the adjacent striatum of tgHD rats. There was no evidence for neuronal maturation and survival of these striatal neuroblasts. Therefore, the functional role of these invading neuroblasts still needs to be determined, but they might offer an endogenous alternative for stem or neuronal cell transplantation strategies. Public Library of Science 2015-02-26 /pmc/articles/PMC4342015/ /pubmed/25719447 http://dx.doi.org/10.1371/journal.pone.0116069 Text en © 2015 Kandasamy et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Kandasamy, Mahesh
Rosskopf, Michael
Wagner, Katrin
Klein, Barbara
Couillard-Despres, Sebastien
Reitsamer, Herbert A.
Stephan, Michael
Nguyen, Huu Phuc
Riess, Olaf
Bogdahn, Ulrich
Winkler, Jürgen
von Hörsten, Stephan
Aigner, Ludwig
Reduction in Subventricular Zone-Derived Olfactory Bulb Neurogenesis in a Rat Model of Huntington’s Disease Is Accompanied by Striatal Invasion of Neuroblasts
title Reduction in Subventricular Zone-Derived Olfactory Bulb Neurogenesis in a Rat Model of Huntington’s Disease Is Accompanied by Striatal Invasion of Neuroblasts
title_full Reduction in Subventricular Zone-Derived Olfactory Bulb Neurogenesis in a Rat Model of Huntington’s Disease Is Accompanied by Striatal Invasion of Neuroblasts
title_fullStr Reduction in Subventricular Zone-Derived Olfactory Bulb Neurogenesis in a Rat Model of Huntington’s Disease Is Accompanied by Striatal Invasion of Neuroblasts
title_full_unstemmed Reduction in Subventricular Zone-Derived Olfactory Bulb Neurogenesis in a Rat Model of Huntington’s Disease Is Accompanied by Striatal Invasion of Neuroblasts
title_short Reduction in Subventricular Zone-Derived Olfactory Bulb Neurogenesis in a Rat Model of Huntington’s Disease Is Accompanied by Striatal Invasion of Neuroblasts
title_sort reduction in subventricular zone-derived olfactory bulb neurogenesis in a rat model of huntington’s disease is accompanied by striatal invasion of neuroblasts
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4342015/
https://www.ncbi.nlm.nih.gov/pubmed/25719447
http://dx.doi.org/10.1371/journal.pone.0116069
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