Impaired Expression of GABA Signaling Components in the Alzheimer’s Disease Middle Temporal Gyrus

International Journal of Molecular Sciences

Karan Govindpani¹  Andrea Kwakowsky¹  Clinton Turner¹  HenryJ Waldvogel¹  RichardL M Faull¹ 

[1] Centre for Brain Research, Department of Anatomy and Medical Imaging, Faculty of Medical and Health Sciences, University of Auckland, Auckland 1023, New Zealand;

关键词: Alzheimer’s disease;    GABA;    GABAergic system;    GABA receptors;    GABA transporters;    middle temporal gyrus;   

DOI  :  10.3390/ijms21228704

来源: DOAJ

【 摘 要 】

γ-aminobutyric acid (GABA) is the primary inhibitory neurotransmitter, playing a central role in the regulation of cortical excitability and the maintenance of the excitatory/inhibitory (E/I) balance. Several lines of evidence point to a remodeling of the cerebral GABAergic system in Alzheimer’s disease (AD), with past studies demonstrating alterations in GABA receptor and transporter expression, GABA synthesizing enzyme activity and focal GABA concentrations in post-mortem tissue. AD is a chronic neurodegenerative disorder with a poorly understood etiology and the temporal cortex is one of the earliest regions in the brain to be affected by AD neurodegeneration. Utilizing NanoString nCounter analysis, we demonstrate here the transcriptional downregulation of several GABA signaling components in the post-mortem human middle temporal gyrus (MTG) in AD, including the GABA_A receptor α₁, α₂, α₃, α₅, β₁, β₂, β₃, δ, γ₂, γ₃, and θ subunits and the GABA_B receptor 2 (GABA_BR2) subunit. In addition to this, we note the transcriptional upregulation of the betaine-GABA transporter (BGT1) and GABA transporter 2 (GAT2), and the downregulation of the 67 kDa isoform of glutamate decarboxylase (GAD₆₇), the primary GABA synthesizing enzyme. The functional consequences of these changes require further investigation, but such alterations may underlie disruptions to the E/I balance that are believed to contribute to cognitive decline in AD.

【 授权许可】

Unknown