title: Neuroendocrine and neurotrophic signaling in Huntington's disease: Implications for pathogenic mechanisms and treatment strategies.
abstract: Huntington's disease (HD) is a fatal neurodegenerative disease caused by an extended polyglutamine tract in the huntingtin protein. Circadian, sleep and hypothalamic-pituitary-adrenal (HPA) axis disturbances are observed in HD as early as 15 years before clinical disease onset. Disturbances in these key processes result in increased cortisol and altered melatonin release which may negatively impact on brain-derived neurotrophic factor (BDNF) expression and contribute to documented neuropathological and clinical disease features. This review describes the normal interactions between neurotrophic factors, the HPA-axis and circadian rhythm, as indicated by levels of BDNF, cortisol and melatonin, and the alterations in these intricately balanced networks in HD. We also discuss the implications of these alterations on the neurobiology of HD and the potential to result in hypothalamic, circadian, and sleep pathologies. Measurable alterations in these pathways provide targets that, if treated early, may reduce degeneration of brain structures. We therefore focus here on the means by which multidisciplinary therapy could be utilised as a non-pharmaceutical approach to restore the balance of these pathways.
authors.affiliation: School of Medical and Health Sciences, Edith Cowan University, 270 Joondalup Drive, Perth, Australia. Electronic address: d.bartlett@ecu.edu.au.
authors.forename: Danielle M
authors.initials: DM
authors.lastname: Bartlett
authors.affiliation: School of Medical and Health Sciences, Edith Cowan University, 270 Joondalup Drive, Perth, Australia.
authors.forename: Travis M
authors.initials: TM
authors.lastname: Cruickshank
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, Kenneth Myer Building, University of Melbourne, 30 Royal Parade, Parkville, Australia.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Hannan
authors.affiliation: Centre for Sleep Science, School of Anatomy, Physiology and Human Biology, University of Western Australia, 10-12 Parkway Drive, Perth, Western Australia, Australia.
authors.forename: Peter R
authors.initials: PR
authors.lastname: Eastwood
authors.affiliation: John van Geest Centre for Brain Repair, Department of Clinical Neurosciences, University of Cambridge, Forvie Site, Robinson Way, Cambridge, UK.
authors.forename: Alpar S
authors.initials: AS
authors.lastname: Lazar
authors.affiliation: School of Medical and Health Sciences, Edith Cowan University, 270 Joondalup Drive, Perth, Australia; School of Pathology and Laboratory Medicine, University of Western Australia, 35 Stirling Highway, Perth, Australia.
authors.forename: Mel R
authors.initials: MR
authors.lastname: Ziman
mesh_terms: D019208:Brain-Derived Neurotrophic Factor; D006801:Humans; D006816:Huntington Disease; D007030:Hypothalamo-Hypophyseal System; D007031:Hypothalamus; D010913:Pituitary-Adrenal System
chemical_list: D019208:Brain-Derived Neurotrophic Factor
keywords: Brain-derived neurotrophic factor (BDNF); Circadian rhythm; Hypothalamic-pituitary-adrenal (HPA) axis; Hypothalamus; Sleep; Suprachiasmatic nucleus (SCN)