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• W1762953213 abstract "Despite the well established central pathophysiology of Huntington’s disease (HD), less is known about systemic impairments that are emerging as significant contributors to the morbidity of this neurodegenerative condition. Given the evidence of neuroendocrine dysfunction in HD patients and the pro-neural properties of sex-hormones, we explored the therapeutic potential of hormone therapy in the HD R6/1 mouse model (HD mice). HD mice over-express exon-1 of the defective human HD gene and replicate many of the clinical behavioural, biochemical and physiological impairments. Seven-week-old HD and wild-type littermate mice had either saline (control) or testosterone (treatment; 160 μg/day over 90 days) pellets implanted s.c. and were subsequently subjected to behavioural, molecular and cellular analysis. Separate mice were used to establish a decrease in serum testosterone concentrations in HD mice at 12 weeks of age. Baseline serum testosterone was significantly reduced in control 19-week-old HD mice, whereas treatment significantly raised serum testosterone in both wild-type and HD mice. Testosterone treatment had a limited effect on the development of rotarod deficiencies in HD mice and no effect on progressive body weight loss or the development of central mutant huntingtin-containing aggregates. Testosterone treatment induced hypo-locomotion in both genotypes. Deficits in hippocampal-dependent cognition and neurogenesis were not rescued in testosterone-treated HD mice. By contrast, wild-type-treatment mice experienced significantly increased neuronal survival and differentiation. Testosterone treatment in HD mice did rescue androgen receptor levels in the hippocampus and testes, significantly improved severe testicular atrophy and restored spermatogenesis. We conclude that chronic testosterone provides systemic efficacy in treating spermatogenesis deficits and testicular atrophy but not central cellular and behavioural pathologies in R6/1 HD mice." @default.
• W1762953213 created "2016-06-24" @default.
• W1762953213 creator A5006071075 @default.
• W1762953213 creator A5052976583 @default.
• W1762953213 date "2012-01-17" @default.
• W1762953213 modified "2023-09-23" @default.
• W1762953213 title "Deficits in Spermatogenesis but not Neurogenesis are Alleviated by Chronic Testosterone Therapy in R6/1 Huntington’s Disease Mice" @default.
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• W1762953213 doi "https://doi.org/10.1111/j.1365-2826.2011.02238.x" @default.
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