Introduction Huntington’s disease (HD) is an autosomal dominant neurodegenerative disease caused by polyglutamine repeat expansion in the Huntington ‘htt’ gene. HD is characterised by motor and cognitive impairment. Motor abnormalities: chorea and athetosis, deterioration in cognitive function, behavioural changes and a mood component are common symptoms in the presentation of HD. Clinical observation has shown that Huntington’s patients also experience extreme temperature variance during the course of the disease.
Objective To perform a literature review into the possible causes of defective thermoregulation in HD and highlight recent scientific and clinical findings.
Methods AMED, EMBASE, MEDLINE, PsycINFO, BNI,CINAHL databases were searched for relevant papers over the last 10 years. 14 were found but only 3 are directly related to thermoregulation in HD (murine studies, case reports) during this time frame and have been included in this review.
Results Articles reviewed:
D. Gassbeek, et al. Drug-induced hyperthermia in Huntington’s disease. J Neurol2004;251:454-457
Weydt P. et al., Thermoregulatory and metabolic defects in Huntington’s disease transgenic mice implicate PGC-1alpha in Huntington’s disease neurodegeneration. Cell Metabolism2006;4:349-362 DOI:10.1016/j.cmet.2006.10.004
Renoir T,et al. Sexually dimorphic serotonergic dysfunction in a mouse model of Huntington’s disease and depression. PLoS One2011;6(7):e22133
Discussion Using the parameters mentioned in the methods section we reviewed three papers concerning thermoregulation in HD over the last 10 years. It appears that information in this niche field is quite limited and experimentation is required to evolve our understanding of the pathogenesis of this fatal disease.
The first article attempts to link the use of psychotropics in the treatment of psychotic symptoms of HD with hyperthermia. The second article explores the profound thermoregulatory defect in the BAT of HD transgenic mice. Multiple cohorts were tested for adaptative thermogenesis at week 10 and 20 of age with all the test subjects displaying significant reduction in body temperature during the cold challenge. The authors implicate transcriptional interference of PGC-1α in the murine HD BAT and postulate that mitochondrial dysfunction in HD may stem from ployQ-htt interference with PGC-1α in the nucleus linking transcriptional dysregulation with mitochondrial pathology in HD. They propose HD therefore to be a metabolic disease and that PGC-1α dysregulation affiliated with temperature fluctuations in HD.
However, clinical observation yields an inconsistency in the symptoms experienced by patients as some experience hyperthermia and some hypothermia. So far the literature only shows drug induced hyperthermia in HD and murine models of hypothermia. We do not have a unifying concept nor an adequate amount of data and therefore it remains difficult to draw robust conclusions about the causes of temperature dysregulation in HD.
This review highlights the need for further research in this area. Understanding thermoregulation in HD can potentially have great therapeutic value for some patients and would assist clinicians in developing a more robust management plan.
- “Huntington’s Disease”
- “metabolic effect”
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