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

• Published in: PloS one Vol. 11; no. 2; p. e0147583
• Main Authors: Kuljis, Dika A, Gad, Laura, Loh, Dawn H, MacDowell Kaswan, Zoë, Hitchcock, Olivia N, Ghiani, Cristina A, Colwell, Christopher S
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 12.02.2016; Public Library of Science (PLoS)
• Subjects: Age; Alzheimer's disease; Animal cognition; Animals; Arginine Vasopressin - genetics; Arginine Vasopressin - metabolism; Argipressin; Artificial chromosomes; Bacteria; Biological clocks; Biology and Life Sciences; Brain research; Chromosomes, Artificial, Bacterial - genetics; Circadian rhythm; Circadian Rhythm - genetics; Circadian rhythms; Dementia; Disease Models, Animal; Disease Progression; Epidemiology; Female; Females; Founder Effect; Gender aspects; Gender differences; Gene Expression; Hereditary diseases; Humans; Huntington Disease - genetics; Huntington Disease - metabolism; Huntington Disease - pathology; Huntington Disease - physiopathology; Huntington's disease; Huntingtons disease; Intestine; Laboratory animals; Male; Males; Medicine and Health Sciences; Metabolism; Mice; Mice, Transgenic - genetics; Motor Activity; Neurodegeneration; Neurodegenerative diseases; Neurosciences; Physiology; Psychiatry; Research and Analysis Methods; Rodents; Rotarod Performance Test; Sex; Sex differences; Sex Factors; Sleep; Suprachiasmatic nucleus; Suprachiasmatic Nucleus - abnormalities; Suprachiasmatic Nucleus - metabolism; Suprachiasmatic Nucleus - physiopathology; Time Factors; Transgenic mice; Vasoactive agents; Vasoactive intestinal peptide; Vasoactive Intestinal Peptide - genetics; Vasoactive Intestinal Peptide - metabolism; Vasopressin; Los Angeles California; United States > US; California
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0147583

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.