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

International Journal of Molecular Sciences
Karan GovindpaniAndrea Kwakowsky

Abstract

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 GABAA receptor α1, α2, α3, α5, β1, β2, β3, δ, γ2, γ3, and θ subunits and the GABAB receptor 2 (GABABR2) 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 f...Continue Reading

References

Apr 10, 1992·Science·J A Hardy, G A Higgins
Jan 1, 1991·Acta Neuropathologica·H Braak, E Braak
Jan 1, 1987·Journal of Neuropathology and Experimental Neurology·J A DoeblerR E Rhoads
Mar 1, 1988·Journal of the Neurological Sciences·K J ReinikainenP J Riekkinen
Jan 1, 1988·Journal of Neural Transmission·M D SimpsonJ F Deakin
Nov 1, 1986·Annals of Neurology·D W EllisonJ B Martin
Jul 1, 1986·Proceedings of the National Academy of Sciences of the United States of America·I Grundke-IqbalL I Binder
Aug 1, 1988·Brain : a Journal of Neurology·S L LoweD M Bowen
Jan 14, 1987·Neuroscience Letters·J HardyB Winblad
Jul 1, 1985·Proceedings of the National Academy of Sciences of the United States of America·R C PearsonT P Powell
Mar 31, 1984·British Medical Journal·M N RossorM Roth
Jun 1, 1982·Brain : a Journal of Neurology·M N RossorL L Iversen
Feb 1, 1981·Journal of Neurochemistry·T L PerryS S Gandham
Jan 1, 1994·Annual Review of Neuroscience·R L Macdonald, R W Olsen
Jun 10, 1997·Proceedings of the National Academy of Sciences of the United States of America·H AsadaK Obata
Aug 18, 1999·Proceedings of the National Academy of Sciences of the United States of America·T P BonnertP J Whiting
Oct 27, 1999·Proceedings of the National Academy of Sciences of the United States of America·N TianR Nicoll
Jan 29, 2000·Journal of Neural Transmission·K NäggaJ Marcusson
Feb 24, 2001·Naunyn-Schmiedeberg's Archives of Pharmacology·R SeidlG Lubec
Mar 21, 2002·Acta Neuropathologica·Marcus RösslerThomas G Ohm
Apr 4, 2002·Proceedings of the National Academy of Sciences of the United States of America·Rachael I ScahillNick C Fox
Aug 13, 2002·Current Topics in Medicinal Chemistry·W Sieghart, G Sperk
Sep 25, 2003·Journal of Neuropathology and Experimental Neurology·Susanne PirkerGünther Sperk
Jul 20, 2004·The Journal of Biological Chemistry·Joseph SimonEric A Barnard

❮ Previous
Next ❯

Citations

May 11, 2021·Frontiers in Cell and Developmental Biology·Longxiu YangChongdong Jian
Jun 15, 2021·Frontiers in Aging Neuroscience·Shaochang WuZongxin Ling
Aug 22, 2021·Journal, Genetic Engineering & Biotechnology·Amr GhitDiaa Eldin E Hussein

❮ Previous
Next ❯

Methods Mentioned

BETA
dissection
Fluorescence

Software Mentioned

nCounter
Custom CodeSet
nSolver
NanoString nCounter

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.