Mood alterations in mouse models of Spinocerebellar Ataxia type 1

Abstract Spinocerebellar ataxia type 1 (SCA1) is a fatal neurodegenerative disease caused by abnormal expansion of glutamine-encoding CAG repeats in the Ataxin-1 (ATXN1) gene. SCA1 is characterized by progressive motor deficits, cognitive decline, and mood changes including anxiety and depression, w...

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Autores principales:	Melissa Asher, Juao-Guilherme Rosa, Marija Cvetanovic
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/621e832c225f4b51b497deb29caef4aa
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spelling	oai:doaj.org-article:621e832c225f4b51b497deb29caef4aa2021-12-02T14:01:23ZMood alterations in mouse models of Spinocerebellar Ataxia type 110.1038/s41598-020-80664-92045-2322https://doaj.org/article/621e832c225f4b51b497deb29caef4aa2021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-80664-9https://doaj.org/toc/2045-2322Abstract Spinocerebellar ataxia type 1 (SCA1) is a fatal neurodegenerative disease caused by abnormal expansion of glutamine-encoding CAG repeats in the Ataxin-1 (ATXN1) gene. SCA1 is characterized by progressive motor deficits, cognitive decline, and mood changes including anxiety and depression, with longer number of repeats correlating with worse disease outcomes. While mouse models have been very useful in understanding etiology of ataxia and cognitive decline, our understanding of mood symptoms in SCA1 has lagged. It remains unclear whether anxiety or depression stem from an underlying brain pathology or as a consequence of living with an untreatable and lethal disease. To increase our understanding of the etiology of SCA1 mood alterations, we used the elevated-plus maze, sucrose preference and forced swim tests to assess mood in four different mouse lines. We found that SCA1 knock-in mice exhibit increased anxiety that correlated with the length of CAG repeats, supporting the idea that underlying brain pathology contributes to SCA1-like anxiety. Additionally, our results support the concept that increased anxiety is caused by non-cerebellar pathology, as Purkinje cell specific SCA1 transgenic mice exhibit decreased anxiety-like behavior. Regarding the molecular mechanism, partial loss of ATXN1 may play a role in anxiety, based on our results for Atxn1 haploinsufficient and null mice.Melissa AsherJuao-Guilherme RosaMarija CvetanovicNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Melissa Asher Juao-Guilherme Rosa Marija Cvetanovic Mood alterations in mouse models of Spinocerebellar Ataxia type 1
description	Abstract Spinocerebellar ataxia type 1 (SCA1) is a fatal neurodegenerative disease caused by abnormal expansion of glutamine-encoding CAG repeats in the Ataxin-1 (ATXN1) gene. SCA1 is characterized by progressive motor deficits, cognitive decline, and mood changes including anxiety and depression, with longer number of repeats correlating with worse disease outcomes. While mouse models have been very useful in understanding etiology of ataxia and cognitive decline, our understanding of mood symptoms in SCA1 has lagged. It remains unclear whether anxiety or depression stem from an underlying brain pathology or as a consequence of living with an untreatable and lethal disease. To increase our understanding of the etiology of SCA1 mood alterations, we used the elevated-plus maze, sucrose preference and forced swim tests to assess mood in four different mouse lines. We found that SCA1 knock-in mice exhibit increased anxiety that correlated with the length of CAG repeats, supporting the idea that underlying brain pathology contributes to SCA1-like anxiety. Additionally, our results support the concept that increased anxiety is caused by non-cerebellar pathology, as Purkinje cell specific SCA1 transgenic mice exhibit decreased anxiety-like behavior. Regarding the molecular mechanism, partial loss of ATXN1 may play a role in anxiety, based on our results for Atxn1 haploinsufficient and null mice.
format	article
author	Melissa Asher Juao-Guilherme Rosa Marija Cvetanovic
author_facet	Melissa Asher Juao-Guilherme Rosa Marija Cvetanovic
author_sort	Melissa Asher
title	Mood alterations in mouse models of Spinocerebellar Ataxia type 1
title_short	Mood alterations in mouse models of Spinocerebellar Ataxia type 1
title_full	Mood alterations in mouse models of Spinocerebellar Ataxia type 1
title_fullStr	Mood alterations in mouse models of Spinocerebellar Ataxia type 1
title_full_unstemmed	Mood alterations in mouse models of Spinocerebellar Ataxia type 1
title_sort	mood alterations in mouse models of spinocerebellar ataxia type 1
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/621e832c225f4b51b497deb29caef4aa
work_keys_str_mv	AT melissaasher moodalterationsinmousemodelsofspinocerebellarataxiatype1 AT juaoguilhermerosa moodalterationsinmousemodelsofspinocerebellarataxiatype1 AT marijacvetanovic moodalterationsinmousemodelsofspinocerebellarataxiatype1
_version_	1718392142886338560

Mood alterations in mouse models of Spinocerebellar Ataxia type 1

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