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

作　　者：Abraham Rosas-Arellano Argel Estrada-Mondragón Carola A.Mantellero Carlos Tejeda-Guzmán Maite A.Castro 

机构地区：[1]Instituto de Bioquimica y Microbiologia, Facultad de Ciencias, Universidad Austral de Chile, Valdivia, Chile [2]Center for Interdisciplinary Studies on the Nervous System (CISNe), Universidad Austral de Chile, Valdivia, Chile [3]Departamento de Fisiologla, Biofisica y Neurociencias, Cinvestav del IPN, Ciudad de Mexico, Mexico [4]Queensland Brain Institute, The University of Queensland, Brisbane, Australia [5]Laboratorio de Neurociencias, Departamento de Biologia, Facultad de Quimica y Biologla, Universidad de Santiago de Chile, Santiago de Chile Chile

出　　处：《Neural Regeneration Research》2018年第4期584-590,共7页中国神经再生研究（英文版）

基　　金：the programs for the postdoctoral fellowships-Chilean CONICYT-FONDECYT#3140218,Mexican CONACYT#164978 and DID-UACh S-2015-81;Sistema Nacional de Investigadores#58512 to Abraham Rosas-Arellano;supported by USACH PhD fellowship;supported with a PhD fellowship from CONACYT(#299627);FONDECYT grants 1151206 and 1110571 to Maite A.Castro

摘　　要：γ-Aminobutyric acid（GABA）,plays a key role in all stages of life,also is considered the main inhibitory neurotransmitter.GABA 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 regions.The biophysical properties of GABAA tonic inhibition have been related with cellular protection against excitotoxic injury and cell death in presence of excessive excitation.On this basis,GABAA tonic inhibition has been proposed as a potential target for therapeutic intervention of Huntington＇s disease.Huntington＇s disease is a neurodegenerative disorder caused by a genetic mutation of the huntingtin protein.For experimental studies of Huntington＇s disease mouse models have been developed,such as R6/1,R6/2,Hdh Q92,Hdh Q150,as well as YAC128.In all of them,some key experimental reports are focused on neostriatum.The 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 subunits.The 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.γ-Aminobutyric acid（GABA）,plays a key role in all stages of life,also is considered the main inhibitory neurotransmitter.GABA 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 regions.The biophysical properties of GABAA tonic inhibition have been related with cellular protection against excitotoxic injury and cell death in presence of excessive excitation.On this basis,GABAA tonic inhibition has been proposed as a potential target for therapeutic intervention of Huntington＇s disease.Huntington＇s disease is a neurodegenerative disorder caused by a genetic mutation of the huntingtin protein.For experimental studies of Huntington＇s disease mouse models have been developed,such as R6/1,R6/2,Hdh Q92,Hdh Q150,as well as YAC128.In all of them,some key experimental reports are focused on neostriatum.The 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 subunits.The 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 

分 类 号：R742.2[医药卫生—神经病学与精神病学]