Sex Differences in Circadian Dysfunction in the BACHD Mouse Model of Huntington's Disease.

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder that affects men and women in equal numbers, but some epidemiological studies indicate there may be sex differences in disease progression. One of the early symptoms of HD is disruptions in the circadian timing system...

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Main Authors: Dika A Kuljis, Laura Gad, Dawn H Loh, Zoë MacDowell Kaswan, Olivia N Hitchcock, Cristina A Ghiani, Christopher S Colwell
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2016-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC4752447?pdf=render
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author Dika A Kuljis
Laura Gad
Dawn H Loh
Zoë MacDowell Kaswan
Olivia N Hitchcock
Cristina A Ghiani
Christopher S Colwell
author_facet Dika A Kuljis
Laura Gad
Dawn H Loh
Zoë MacDowell Kaswan
Olivia N Hitchcock
Cristina A Ghiani
Christopher S Colwell
author_sort Dika A Kuljis
collection DOAJ
description Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder that affects men and women in equal numbers, but some epidemiological studies indicate there may be sex differences in disease progression. One of the early symptoms of HD is disruptions in the circadian timing system, but it is currently unknown whether sex is a factor in these alterations. Since sex differences in HD could provide important insights to understand cellular and molecular mechanism(s) and designing early intervention strategies, we used the bacterial artificial chromosome transgenic mouse model of HD (BACHD) to examine whether sex differences in circadian behavioral rhythms are detectable in an animal model of the disease. Similar to BACHD males, BACHD females display circadian disruptions at both 3 and 6 months of age; however, deficits to BACHD female mouse activity levels, rhythm precision, and behavioral fragmentation are either delayed or less severe relative to males. These sex differences are associated with a smaller suprachiasmatic nucleus (SCN) in BACHD male mice at age of symptom onset (3 months), but are not associated with sex-specific differences in SCN daytime electrical activity deficits, or peptide expression (arginine vasopressin, vasoactive intestinal peptide) within the SCN. Notably, BACHD females exhibited delayed motor coordination deficits, as measured using rotarod and challenge beam. These findings suggest a sex specific factor plays a role both in non-motor and motor symptom progression for the BACHD mouse.
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spelling doaj.art-3b0f37b69e6b4cd1971e9f5a7525699f2022-12-22T03:19:20ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-01112e014758310.1371/journal.pone.0147583Sex Differences in Circadian Dysfunction in the BACHD Mouse Model of Huntington's Disease.Dika A KuljisLaura GadDawn H LohZoë MacDowell KaswanOlivia N HitchcockCristina A GhianiChristopher S ColwellHuntington's disease (HD) is an autosomal dominant neurodegenerative disorder that affects men and women in equal numbers, but some epidemiological studies indicate there may be sex differences in disease progression. One of the early symptoms of HD is disruptions in the circadian timing system, but it is currently unknown whether sex is a factor in these alterations. Since sex differences in HD could provide important insights to understand cellular and molecular mechanism(s) and designing early intervention strategies, we used the bacterial artificial chromosome transgenic mouse model of HD (BACHD) to examine whether sex differences in circadian behavioral rhythms are detectable in an animal model of the disease. Similar to BACHD males, BACHD females display circadian disruptions at both 3 and 6 months of age; however, deficits to BACHD female mouse activity levels, rhythm precision, and behavioral fragmentation are either delayed or less severe relative to males. These sex differences are associated with a smaller suprachiasmatic nucleus (SCN) in BACHD male mice at age of symptom onset (3 months), but are not associated with sex-specific differences in SCN daytime electrical activity deficits, or peptide expression (arginine vasopressin, vasoactive intestinal peptide) within the SCN. Notably, BACHD females exhibited delayed motor coordination deficits, as measured using rotarod and challenge beam. These findings suggest a sex specific factor plays a role both in non-motor and motor symptom progression for the BACHD mouse.http://europepmc.org/articles/PMC4752447?pdf=render
spellingShingle Dika A Kuljis
Laura Gad
Dawn H Loh
Zoë MacDowell Kaswan
Olivia N Hitchcock
Cristina A Ghiani
Christopher S Colwell
Sex Differences in Circadian Dysfunction in the BACHD Mouse Model of Huntington's Disease.
PLoS ONE
title Sex Differences in Circadian Dysfunction in the BACHD Mouse Model of Huntington's Disease.
title_full Sex Differences in Circadian Dysfunction in the BACHD Mouse Model of Huntington's Disease.
title_fullStr Sex Differences in Circadian Dysfunction in the BACHD Mouse Model of Huntington's Disease.
title_full_unstemmed Sex Differences in Circadian Dysfunction in the BACHD Mouse Model of Huntington's Disease.
title_short Sex Differences in Circadian Dysfunction in the BACHD Mouse Model of Huntington's Disease.
title_sort sex differences in circadian dysfunction in the bachd mouse model of huntington s disease
url http://europepmc.org/articles/PMC4752447?pdf=render
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