Phosphodiesterase 10 inhibition reduces striatal excitotoxicity in the quinolinic acid model of Huntington's disease
作者： Carmela Giampà , Stefano Patassini , Antonella Borreca , Daunia Laurenti , Fabrizia Marullo
DOI: 10.1016/J.NBD.2009.02.014
关键词:
摘要: Decreased activity of cAMP responsive element-binding protein (CREB) is thought to contribute the death striatal medium spiny neurons in Huntington's disease (HD). Therefore, therapies that increase levels activated CREB, may be effective fighting neurodegeneration HD. In this study, we sought determine whether phosphodiesterase type 10 (PDE10A) inhibitor TP10 exerts a neuroprotective effect an excitotoxic model Rats were surgically administered with quinolinic acid into striatum and subsequently treated daily for two or eight weeks. After 2 weeks treatment, lesion size was 52% smaller surviving cell number several times higher than vehicle-treated group. These beneficial effects maintained through 8 treatment also increased significantly CREB neurons, which hypothesized contributing mechanism effect. Our findings suggest PDE10A inhibition as novel approach HD confirm importance disease.
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