The adjustment of γ-aminobutyric acidA tonic subunits in Huntingtons disease: from transcription to translation to synaptic levels into the neostriatum
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 p1-3 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 Huntingtons disease.Huntingtons disease is a neurodegenerative disorder caused by a genetic mutation of the huntingtin protein.For experimental studies of Huntingtons disease mouse models have been developed, such as R6/1, R6/2, HdhQ92, HdhQ150, 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 Huntingtons 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 Huntingtons disease.
GABAA extrasynaptic and perisynaptic γ-aminobutyric acidA receptors striatum R6/1,R6/2,HdhQ92,HdhQ111,HdhQ150,N171-82Q and YAC128 HD transgenics mice models chorea mutant huntingtin inhibitory neurotransmission D1 medium sized spiny neurons D2 medium siz
Abraham Rosas-Arellano Argel Estrada-Mondragón Carola A.Mantellero Carlos Tejeda-Guzmán Maite A.Castro
Instituto de Bioquímica y Microbiología, Facultad de Ciencias, Universidad Austral de Chile, Valdivi Queensland Brain Institute, The University of Queensland, Brisbane, Australia Laboratorio de Neurociencias, Departamento de Biología, Facultad de Química y Biología, Universidad Departamento de Fisiología, Biofísica y Neurociencias, Cinvestav del IPN, Ciudad de México, México Instituto de Bioquímica y Microbiología, Facultad de Ciencias, Universidad Austral de Chile, Valdivi