Phosphodiesterase 10A Inhibition Improves Cortico-Basal Ganglia Function in Huntington’s Disease Models

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• 作者：Vahri Beaumont¹ ; ⁹ ; ^{vahri.beaumont@chdifoundation.org} ; Sheng Zhong² ; Hai Lin² ; WenJin Xu² ; Amyaouch Bradaia³ ; Esther Steidl³ ; Melanie Gleyzes³ ; Kristian Wadel³ ; Bruno Buisson³ ; Fernando E. Padovan-Neto⁴ ; Shreaya Chakroborty⁴ ; Karen M. Ward⁵ ; John F. Harms⁵ ; Jose Beltran² ; Mei Kwan² ; Afshin Ghavami² ; Jenny Hä ; ggkvist⁶ ; Mikló ; s Tó ; th⁶ ; Christer Halldin⁶ ; Andrea Varrone⁶ ; Christoph Schaab⁷ ; J. Nikolaj Dybowski⁷ ; Sarah Elschenbroich⁷ ; Kimmo Lehtimä ; ki⁸ ; Taneli Heikkinen⁸ ; Larry Park¹ ; James Rosinski¹ ; Ladislav Mrzljak¹ ; Daniel Lavery¹ ; Anthony R. West⁴ ; Christopher J. Schmidt⁵ ; Margaret M. Zaleska⁵ ; Ignacio Munoz-Sanjuan¹
• 关键词：Q175 ; R6/2 ; PDE10A ; corticostriatal ; subthalamic nucleus ; cAMP ; cGMP ; cyclic nucleotide ; PF-02545920 ; MP-10
• 刊名：Neuron
• 出版年：2016
• 出版时间：21 December 2016
• 年：2016
• 卷：92
• 期：6
• 页码：1220-1237
• 全文大小：4833 K
• 卷排序：92

文摘

Q175 and R6/2 HD models exhibit reduced PDE10A equivalent to manifest HD patients PDE10 inhibition restored striatal input and indirect pathway output in HD mice Both cAMP and cGMP elevation were required for rescue Chronic dosing of HD models from pre-symptomatic ages confers additional benefit