title: Sex Differences in Circadian Dysfunction in the BACHD Mouse Model of Huntington's Disease.
abstract: 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.
authors.affiliation: Department of Neurobiology, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Dika A
authors.initials: DA
authors.lastname: Kuljis
authors.affiliation: Department of Psychiatry & Biobehavioral Sciences, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Laura
authors.initials: L
authors.lastname: Gad
authors.affiliation: Department of Psychiatry & Biobehavioral Sciences, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Dawn H
authors.initials: DH
authors.lastname: Loh
authors.affiliation: Department of Psychiatry & Biobehavioral Sciences, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Zoë
authors.initials: Z
authors.lastname: MacDowell Kaswan
authors.affiliation: Department of Psychiatry & Biobehavioral Sciences, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Olivia N
authors.initials: ON
authors.lastname: Hitchcock
authors.affiliation: Department of Psychiatry & Biobehavioral Sciences, University of California Los Angeles, Los Angeles, California, United States of America.|Department of Pathology and Laboratory Medicine, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Cristina A
authors.initials: CA
authors.lastname: Ghiani
authors.affiliation: Department of Psychiatry & Biobehavioral Sciences, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Colwell
mesh_terms: D000818:Animals; D001127:Arginine Vasopressin / Q000235:genetics / Q000378:metabolism; D022202:Chromosomes, Artificial, Bacterial / Q000235:genetics; D002940:Circadian Rhythm / Q000235:genetics*; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D018703:Founder Effect; D015870:Gene Expression; D006801:Humans; D006816:Huntington Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics*; D009043:Motor Activity; D045442:Rotarod Performance Test; D012737:Sex Factors; D013493:Suprachiasmatic Nucleus / Q000002:abnormalities / Q000378:metabolism / Q000503:physiopathology*; D013997:Time Factors; D014660:Vasoactive Intestinal Peptide / Q000235:genetics / Q000378:metabolism
chemical_list: D001127:Arginine Vasopressin; D014660:Vasoactive Intestinal Peptide