title: Ethological endophenotypes are altered by elevated stress hormone levels in both Huntington's disease and wildtype mice.
abstract: Huntington's disease (HD) is an autosomal dominant, neurodegenerative disorder with cognitive, psychiatric, motor, neuroendocrine and peripheral dysfunctions. Symptom onset and progression can be closely modeled in HD transgenic mice, which facilitate the search for therapeutics and environmental modulators. In the first investigation of chronic stress in HD, we have previously shown that administering a moderate dose of the stress hormone, corticosterone (CORT) had no effect on short-term memory in wildtype (WT) mice but accelerated the onset of the impairment in male R6/1 HD mice. We now extend this investigation to ethological dysfunctions in HD, which we hypothesized to be more susceptible to CORT treatment compared to the same functions in WT littermates. Both genotypes consumed similar doses of CORT dissolved in drinking water across 6-14 weeks of age and were assessed for olfactory sensitivity, nest-building, saccharin preference as well as vocal responses to sociosexual stimuli. In female HD and WT mice, olfactory sensitivity and saccharin preference were reduced by 2 and 4 weeks of CORT, respectively. In males, there was no effect of CORT on saccharin preference, however the number of vocalizations to a female mouse was transiently increased by CORT-drinking, regardless of genotype. Nest-building was severely impaired in HD mice at an early age, but was unaffected by CORT. Our results suggest that the presence of the HD mutation had no bearing on CORT-induced effects at this dose, suggesting that even moderately elevated stress hormone levels can impair ethological behaviors in both the HD and healthy brain.
authors.affiliation: Florey Institute of Neuroscience and Mental Health, Kenneth Myer Building, University of Melbourne, Parkville, Australia; Department of Anatomy and Neuroscience, University of Melbourne, Parkville, Australia. Electronic address: christina.mo@unimelb.edu.au.
authors.forename: Christina
authors.initials: C
authors.lastname: Mo
authors.affiliation: Florey Institute of Neuroscience and Mental Health, Kenneth Myer Building, University of Melbourne, Parkville, Australia. Electronic address: thibault.renoir@unimelb.edu.au.
authors.forename: Thibault
authors.initials: T
authors.lastname: Renoir
authors.affiliation: Florey Institute of Neuroscience and Mental Health, Kenneth Myer Building, University of Melbourne, Parkville, Australia; Department of Anatomy and Neuroscience, University of Melbourne, Parkville, Australia.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Hannan
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology; D003345:Corticosterone / Q000008:administration & dosage* / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D058068:Endophenotypes; D005260:Female; D005518:Food Preferences / Q000187:drug effects / Q000502:physiology; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000150:complications / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins; D009425:Nesting Behavior / Q000187:drug effects; D009687:Nuclear Proteins; D000857:Olfaction Disorders / Q000188:drug therapy / Q000209:etiology; D012439:Saccharin / Q000008:administration & dosage; D012737:Sex Factors; D018911:Trinucleotide Repeats / Q000235:genetics; D014828:Vocalization, Animal / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; C506812:Htt protein, mouse; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D012439:Saccharin; D003345:Corticosterone
keywords: Corticosterone; Ethological behavior; Gene–environment interactions; Neurodegenerative disease; Olfaction; Sexual behavior; Stress hormone; Tandem repeat disorder; Vocalizations