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The adjustment of γ-aminobutyric acid_A tonic subunits in Huntington＇s disease：from transcription to translation to synaptic levels into the neostriatum

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Neural Regeneration Research 2018年第4期13卷 584-590页

作者： Abraham Rosas-Arellano Argel Estrada-Mondragón Carola A.Mantellero Carlos Tejeda-Guzmán Maite A.Castro Instituto de Bioquimica y Microbiologia Facultad de Ciencias Universidad Austral de Chile Valdivia Chile Center for Interdisciplinary Studies on the Nervous System (CISNe) Universidad Austral de Chile Valdivia Chile Departamento de Fisiologla Biofisica y Neurociencias Cinvestav del IPN Ciudad de Mexico Mexico Queensland Brain Institute The University of Queensland Brisbane Australia Laboratorio de Neurociencias Departamento de Biologia Facultad de Quimica y Biologla Universidad de Santiago de Chile Santiago de Chile Chile

γ-Aminobutyric acid（GABA）,plays a key role in all stages of life,also is considered the main inhibitory *** activates two kind of membrane receptors known as GABAA and GABAB,the first one is responsible to render tonic inhibition by pentameric receptors containing α4-6,β3,δ,or ρ1-3 subunits,they are located at perisynaptic and/or in extrasynaptic *** biophysical properties of GABAA tonic inhibition have been related with cellular protection against excitotoxic injury and cell death in presence of excessive *** this basis,GABAA tonic inhibition has been proposed as a potential target for therapeutic intervention of Huntington＇s ***＇s disease is a neurodegenerative disorder caused by a genetic mutation of the huntingtin *** experimental studies of Huntington＇s disease mouse models have been developed,such as R6/1,R6/2,Hdh Q92,Hdh Q150,as well as *** all of them,some key experimental reports are focused on *** neostriatum is considered as the most important connection between cerebral cortex and basal ganglia structures,its cytology display two pathways called direct and indirect constituted by medium sized spiny neurons expressing dopamine D1 and D2 receptors respectively,they display strong expression of many types of GABAA receptors,including tonic *** studies about of GABAA tonic subunits and Huntington＇s disease into the neostriatum are rising in recent years,suggesting interesting changes in their expression and localization which can be used as a strategy to delay the cellular damage caused by the imbalance between excitation and inhibition,a hallmark of Huntington＇s disease.

关键词： GABAA extrasynaptic and perisynaptic y-aminobutyric acidA receptors striatum R6/1, R6/2,HdhQ92, HdhQ111, HdhQ150, N171-82Q and YAC128 HD transgenics mice models chorea mutanthuntingtin inhibitory neurotransmission D1 medium sized spiny neurons D2 medium sized spiny neurons

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