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BACHD Mice Recapitulate the Striatal Parvalbuminergic Interneuron Loss Found in Huntington’s Disease
Huntington’s disease (HD) is a dominantly inherited, adult-onset neurodegenerative disease characterized by motor, psychiatric, and cognitive abnormalities. Neurodegeneration is prominently observed in the striatum where GABAergic medium spiny neurons (MSN) are the most affected neuronal population....
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8180558/ https://www.ncbi.nlm.nih.gov/pubmed/34108866 http://dx.doi.org/10.3389/fnana.2021.673177 |
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author | Rallapalle, Vyshnavi King, Annesha C. Gray, Michelle |
author_facet | Rallapalle, Vyshnavi King, Annesha C. Gray, Michelle |
author_sort | Rallapalle, Vyshnavi |
collection | PubMed |
description | Huntington’s disease (HD) is a dominantly inherited, adult-onset neurodegenerative disease characterized by motor, psychiatric, and cognitive abnormalities. Neurodegeneration is prominently observed in the striatum where GABAergic medium spiny neurons (MSN) are the most affected neuronal population. Interestingly, recent reports of pathological changes in HD patient striatal tissue have identified a significant reduction in the number of parvalbumin-expressing interneurons which becomes more robust in tissues of higher disease grade. Analysis of other interneuron populations, including somatostatin, calretinin, and cholinergic, did not reveal significant neurodegeneration. Electrophysiological experiments in BACHD mice have identified significant changes in the properties of parvalbumin and somatostatin expressing interneurons in the striatum. Furthermore, their interactions with MSNs are altered as the mHTT expressing mouse models age with increased input onto MSNs from striatal somatostatin and parvalbumin-expressing neurons. In order to determine whether BACHD mice recapitulate the alterations in striatal interneuron number as observed in HD patients, we analyzed the number of striatal parvalbumin, somatostatin, calretinin, and choline acetyltransferase positive cells in symptomatic 12–14 month-old mice by immunofluorescent labeling. We observed a significant decrease in the number of parvalbumin-expressing interneurons as well as a decrease in the area and perimeter of these cells. No significant changes were observed for somatostatin, calretinin, or cholinergic interneuron numbers while a significant decrease was observed for the area of cholinergic interneurons. Thus, the BACHD mice recapitulate the degenerative phenotype observed in the parvalbumin interneurons in HD patient striata without affecting the number of other interneuron populations in the striatum. |
format | Online Article Text |
id | pubmed-8180558 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-81805582021-06-08 BACHD Mice Recapitulate the Striatal Parvalbuminergic Interneuron Loss Found in Huntington’s Disease Rallapalle, Vyshnavi King, Annesha C. Gray, Michelle Front Neuroanat Neuroscience Huntington’s disease (HD) is a dominantly inherited, adult-onset neurodegenerative disease characterized by motor, psychiatric, and cognitive abnormalities. Neurodegeneration is prominently observed in the striatum where GABAergic medium spiny neurons (MSN) are the most affected neuronal population. Interestingly, recent reports of pathological changes in HD patient striatal tissue have identified a significant reduction in the number of parvalbumin-expressing interneurons which becomes more robust in tissues of higher disease grade. Analysis of other interneuron populations, including somatostatin, calretinin, and cholinergic, did not reveal significant neurodegeneration. Electrophysiological experiments in BACHD mice have identified significant changes in the properties of parvalbumin and somatostatin expressing interneurons in the striatum. Furthermore, their interactions with MSNs are altered as the mHTT expressing mouse models age with increased input onto MSNs from striatal somatostatin and parvalbumin-expressing neurons. In order to determine whether BACHD mice recapitulate the alterations in striatal interneuron number as observed in HD patients, we analyzed the number of striatal parvalbumin, somatostatin, calretinin, and choline acetyltransferase positive cells in symptomatic 12–14 month-old mice by immunofluorescent labeling. We observed a significant decrease in the number of parvalbumin-expressing interneurons as well as a decrease in the area and perimeter of these cells. No significant changes were observed for somatostatin, calretinin, or cholinergic interneuron numbers while a significant decrease was observed for the area of cholinergic interneurons. Thus, the BACHD mice recapitulate the degenerative phenotype observed in the parvalbumin interneurons in HD patient striata without affecting the number of other interneuron populations in the striatum. Frontiers Media S.A. 2021-05-24 /pmc/articles/PMC8180558/ /pubmed/34108866 http://dx.doi.org/10.3389/fnana.2021.673177 Text en Copyright © 2021 Rallapalle, King and Gray. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Neuroscience Rallapalle, Vyshnavi King, Annesha C. Gray, Michelle BACHD Mice Recapitulate the Striatal Parvalbuminergic Interneuron Loss Found in Huntington’s Disease |
title | BACHD Mice Recapitulate the Striatal Parvalbuminergic Interneuron Loss Found in Huntington’s Disease |
title_full | BACHD Mice Recapitulate the Striatal Parvalbuminergic Interneuron Loss Found in Huntington’s Disease |
title_fullStr | BACHD Mice Recapitulate the Striatal Parvalbuminergic Interneuron Loss Found in Huntington’s Disease |
title_full_unstemmed | BACHD Mice Recapitulate the Striatal Parvalbuminergic Interneuron Loss Found in Huntington’s Disease |
title_short | BACHD Mice Recapitulate the Striatal Parvalbuminergic Interneuron Loss Found in Huntington’s Disease |
title_sort | bachd mice recapitulate the striatal parvalbuminergic interneuron loss found in huntington’s disease |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8180558/ https://www.ncbi.nlm.nih.gov/pubmed/34108866 http://dx.doi.org/10.3389/fnana.2021.673177 |
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