Normalizing glucocorticoid levels attenuates metabolic and neuropathological symptoms in the R6/2 mouse model of huntington's disease.

Normalizing glucocorticoid levels attenuates metabolic and neuropathological symptoms in the R6/2 mouse model of huntington's disease. Neurobiol Dis. 2018 Oct 04;: Authors: Dufour BD, McBride JL Abstract Huntington's disease (HD) is a fatal genetic neurological disorder caused by a mutation in the human Huntingtin (HTT) gene. This mutation confers a toxic gain of function of the encoded mutant huntingtin (mHTT) protein, leading to widespread neuropathology including the formation of mHTT-positive inclusion bodies, gene dysregulation, reduced levels of adult dentate gyrus neurogenesis and ultimate neuron loss throughout many regions of the brain. Additionally, because HTT is ubiquitously expressed, several peripheral tissues are also affected. HD patients suffer from progressive motor, cognitive, psychiatric, and metabolic symptoms, including weight loss and skeletal muscle wasting. HD patients also show neuroendocrine changes including a robust, significant elevation in circulating levels of the glucocorticoid, cortisol. Previously, we confirmed that the R6/2 mouse model of HD exhibits elevated corticosterone (the rodent homolog of cortisol) levels and demonstrated that experimentally elevated corticosterone exacerbates R6/2 HD symptomology, resulting in severe and rapid weight loss and a shorter latency to death. Given that efficacious therapeutics are lacking for HD, here we investigated whether normalizing glucocorticoid levels co...
Source: Neurobiology of Disease - Category: Neurology Authors: Tags: Neurobiol Dis Source Type: research