Maintenance of basal levels of autophagy in Huntington's disease mouse models displaying metabolic dysfunction.

Huntington's disease (HD) is a fatal neurodegenerative disorder caused by an expanded polyglutamine repeat in the huntingtin protein. Neuropathology in the basal ganglia and in the cerebral cortex has been linked to the motor and cognitive symptoms whereas recent work has suggested that the hyp...

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Autores principales:	Barbara Baldo, Rana Soylu, Asa Petersén
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5f193679e8fa4998bc8932e1e76bb743
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spelling	oai:doaj.org-article:5f193679e8fa4998bc8932e1e76bb7432021-11-18T08:40:56ZMaintenance of basal levels of autophagy in Huntington's disease mouse models displaying metabolic dysfunction.1932-620310.1371/journal.pone.0083050https://doaj.org/article/5f193679e8fa4998bc8932e1e76bb7432013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24376631/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Huntington's disease (HD) is a fatal neurodegenerative disorder caused by an expanded polyglutamine repeat in the huntingtin protein. Neuropathology in the basal ganglia and in the cerebral cortex has been linked to the motor and cognitive symptoms whereas recent work has suggested that the hypothalamus might be involved in the metabolic dysfunction. Several mouse models of HD that display metabolic dysfunction have hypothalamic pathology, and expression of mutant huntingtin in the hypothalamus has been causally linked to the development of metabolic dysfunction in mice. Although the pathogenic mechanisms by which mutant huntingtin exerts its toxic functions in the HD brain are not fully known, several studies have implicated a role for the lysososomal degradation pathway of autophagy. Interestingly, changes in autophagy in the hypothalamus have been associated with the development of metabolic dysfunction in wild-type mice. We hypothesized that expression of mutant huntingtin might lead to changes in the autophagy pathway in the hypothalamus in mice with metabolic dysfunction. We therefore investigated whether there were changes in basal levels of autophagy in a mouse model expressing a fragment of 853 amino acids of mutant huntingtin selectively in the hypothalamus using a recombinant adeno-associate viral vector approach as well as in the transgenic BACHD mice. We performed qRT-PCR and Western blot to investigate the mRNA and protein expression levels of selected autophagy markers. Our results show that basal levels of autophagy are maintained in the hypothalamus despite the presence of metabolic dysfunction in both mouse models. Furthermore, although there were no major changes in autophagy in the striatum and cortex of BACHD mice, we detected modest, but significant differences in levels of some markers in mice at 12 months of age. Taken together, our results indicate that overexpression of mutant huntingtin in mice do not significantly perturb basal levels of autophagy.Barbara BaldoRana SoyluAsa PetersénPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 12, p e83050 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Barbara Baldo Rana Soylu Asa Petersén Maintenance of basal levels of autophagy in Huntington's disease mouse models displaying metabolic dysfunction.
description	Huntington's disease (HD) is a fatal neurodegenerative disorder caused by an expanded polyglutamine repeat in the huntingtin protein. Neuropathology in the basal ganglia and in the cerebral cortex has been linked to the motor and cognitive symptoms whereas recent work has suggested that the hypothalamus might be involved in the metabolic dysfunction. Several mouse models of HD that display metabolic dysfunction have hypothalamic pathology, and expression of mutant huntingtin in the hypothalamus has been causally linked to the development of metabolic dysfunction in mice. Although the pathogenic mechanisms by which mutant huntingtin exerts its toxic functions in the HD brain are not fully known, several studies have implicated a role for the lysososomal degradation pathway of autophagy. Interestingly, changes in autophagy in the hypothalamus have been associated with the development of metabolic dysfunction in wild-type mice. We hypothesized that expression of mutant huntingtin might lead to changes in the autophagy pathway in the hypothalamus in mice with metabolic dysfunction. We therefore investigated whether there were changes in basal levels of autophagy in a mouse model expressing a fragment of 853 amino acids of mutant huntingtin selectively in the hypothalamus using a recombinant adeno-associate viral vector approach as well as in the transgenic BACHD mice. We performed qRT-PCR and Western blot to investigate the mRNA and protein expression levels of selected autophagy markers. Our results show that basal levels of autophagy are maintained in the hypothalamus despite the presence of metabolic dysfunction in both mouse models. Furthermore, although there were no major changes in autophagy in the striatum and cortex of BACHD mice, we detected modest, but significant differences in levels of some markers in mice at 12 months of age. Taken together, our results indicate that overexpression of mutant huntingtin in mice do not significantly perturb basal levels of autophagy.
format	article
author	Barbara Baldo Rana Soylu Asa Petersén
author_facet	Barbara Baldo Rana Soylu Asa Petersén
author_sort	Barbara Baldo
title	Maintenance of basal levels of autophagy in Huntington's disease mouse models displaying metabolic dysfunction.
title_short	Maintenance of basal levels of autophagy in Huntington's disease mouse models displaying metabolic dysfunction.
title_full	Maintenance of basal levels of autophagy in Huntington's disease mouse models displaying metabolic dysfunction.
title_fullStr	Maintenance of basal levels of autophagy in Huntington's disease mouse models displaying metabolic dysfunction.
title_full_unstemmed	Maintenance of basal levels of autophagy in Huntington's disease mouse models displaying metabolic dysfunction.
title_sort	maintenance of basal levels of autophagy in huntington's disease mouse models displaying metabolic dysfunction.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/5f193679e8fa4998bc8932e1e76bb743
work_keys_str_mv	AT barbarabaldo maintenanceofbasallevelsofautophagyinhuntingtonsdiseasemousemodelsdisplayingmetabolicdysfunction AT ranasoylu maintenanceofbasallevelsofautophagyinhuntingtonsdiseasemousemodelsdisplayingmetabolicdysfunction AT asapetersen maintenanceofbasallevelsofautophagyinhuntingtonsdiseasemousemodelsdisplayingmetabolicdysfunction
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Maintenance of basal levels of autophagy in Huntington's disease mouse models displaying metabolic dysfunction.

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