P-MD015. Vitamin D intake enhances vitamin D receptor expression in the striatum and rescues memory and motor dysfunction in mouse model huntington’s disease

Abstract

Introduction . A coordinated neuronal network between cortex and the basal ganglia is required for normal motor function, which gets severely impaired in Huntington’s disease (HD). In particular, the selective loss of medium spiny neurons in the striatum is considered as a prime brain region responsible for movement disability observed in HD. In this regard, we explored whether high Vitamin D (VD) supplementation shows neuroprotection in 3- nitropropionic acid induced mouse model of HD (3-NP; 75 mg/kg) as described previously (Fernagut et al., 2002). Methods . Male C57BL/6J mice (3–4 months old) were divided following groups: Vehicle (group I), 3-nitropropionic acid (HD induced group, intraperitoneal injection), only VD supplemented (group III, 500IU/kg) and 3-NP + VD supplementation (group IV). Animals were then subjected to various behavioral tests like locomotion, gait analysis, Morris water maze (MWM) and rota- rod analysis. After 30 days, animals were decapitated and striatal tissues were isolated to check the mRNA expression of nerve growth factor (NGF), brain derived neurotrophic factor (BDNF) and Vitamin D receptor (VDR). Results . Our behavior and mRNA data shows that VD intake significantly rescued striatal functions like motor co-ordination, locomotion and memory known to be severely impaired in HD. Our results also indicate that VD mediated downstream neuroprotective pathomolecular pathway involves increase expression of Vitamin D receptor (VDR) and neurotrophic factors like NGF and BDNF in the striatum. Conclusion . Altogether, we show that Vitamin D can be a potential “Biodrug†to rescue neurodegeneration as observed in Huntington's Disease.