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The cholinergic and glutamatergic neurotransmission systems are known to be severely disrupted in Alzheimer's disease (AD). GABAergic neurotransmission, in contrast, is generally thought to be well preserved. Evidence from animal models and human postmortem tissue suggest GABAergic remodeling in the AD brain. Nevertheless, there is no information on changes, if any, in the electrophysiological properties of human native GABA receptors as a consequence of AD. To gain such information, we have microtransplanted cell membranes, isolated from temporal cortices of control and AD brains, into Xenopus oocytes, and recorded the electrophysiological activity of the transplanted GABA receptors. We found an age-dependent reduction of GABA currents in the AD brain. This reduction was larger when the AD membranes were obtained from younger subjects. We also found that GABA currents from AD brains have a faster rate of desensitization than those from non-AD brains. Furthermore, GABA receptors from AD brains were slightly, but significantly, less sensitive to GABA than receptors from non-AD brains. The reduction of GABA currents in AD was associated with reductions of mRNA and protein of the principal GABA receptor subunits normally present in the temporal cortex. Pairwise analysis of the transcripts within control and AD groups and analyses of the proportion of GABA receptor subunits revealed down-regulation of α1 and γ2 subunits in AD. In contrast, the proportions of α2, β1, and γ1 transcripts were up-regulated in the AD brains. Our data support a functional remodeling of GABAergic neurotransmission in the human AD brain.
Agarwal,
Reduced expression of the inhibitory synapse scaffolding protein gephyrin in Alzheimer's disease.
2008, Pubmed
Agarwal,
Reduced expression of the inhibitory synapse scaffolding protein gephyrin in Alzheimer's disease.
2008,
Pubmed Allen,
Biochemical evidence of selective nerve cell changes in the normal ageing human and rat brain.
1983,
Pubmed Armstrong,
AMPA-selective glutamate receptor subtype immunoreactivity in the entorhinal cortex of non-demented elderly and patients with Alzheimer's disease.
1994,
Pubmed Barish,
A transient calcium-dependent chloride current in the immature Xenopus oocyte.
1983,
Pubmed
,
Xenbase Bernareggi,
Properties of glutamate receptors of Alzheimer's disease brain transplanted to frog oocytes.
2007,
Pubmed Bonnert,
theta, a novel gamma-aminobutyric acid type A receptor subunit.
1999,
Pubmed
,
Xenbase Coleman,
Neuron numbers and dendritic extent in normal aging and Alzheimer's disease.
1987,
Pubmed Cosenza-Nashat,
Expression of the translocator protein of 18 kDa by microglia, macrophages and astrocytes based on immunohistochemical localization in abnormal human brain.
2009,
Pubmed Dickstein,
Changes in the structural complexity of the aged brain.
2007,
Pubmed Di Lazzaro,
Motor cortex hyperexcitability to transcranial magnetic stimulation in Alzheimer's disease.
2004,
Pubmed Fraser,
GABAA/benzodiazepine receptors in acutely isolated hippocampal astrocytes.
1995,
Pubmed Fritschy,
Gephyrin: where do we stand, where do we go?
2008,
Pubmed Gallacher,
Benzodiazepine use and risk of dementia: evidence from the Caerphilly Prospective Study (CaPS).
2012,
Pubmed Garcia-Marin,
Diminished perisomatic GABAergic terminals on cortical neurons adjacent to amyloid plaques.
2009,
Pubmed Gong,
Disruption of glutamate receptors at Shank-postsynaptic platform in Alzheimer's disease.
2009,
Pubmed Hof,
The aging brain: morphomolecular senescence of cortical circuits.
2004,
Pubmed Huntsman,
Fast IPSCs in rat thalamic reticular nucleus require the GABAA receptor beta1 subunit.
2006,
Pubmed Iwakiri,
An immunohistochemical study of GABA A receptor gamma subunits in Alzheimer's disease hippocampus: relationship to neurofibrillary tangle progression.
2009,
Pubmed Jesse,
Glial fibrillary acidic protein and protein S-100B: different concentration pattern of glial proteins in cerebrospinal fluid of patients with Alzheimer's disease and Creutzfeldt-Jakob disease.
2009,
Pubmed Khom,
Pharmacological properties of GABAA receptors containing gamma1 subunits.
2006,
Pubmed
,
Xenbase Lanctôt,
GABAergic function in Alzheimer's disease: evidence for dysfunction and potential as a therapeutic target for the treatment of behavioural and psychological symptoms of dementia.
2004,
Pubmed Liepert,
Motor cortex disinhibition in Alzheimer's disease.
2001,
Pubmed Limon,
Microtransplantation of neurotransmitter receptors from postmortem autistic brains to Xenopus oocytes.
2008,
Pubmed
,
Xenbase Livak,
Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method.
2001,
Pubmed Loerch,
Evolution of the aging brain transcriptome and synaptic regulation.
2008,
Pubmed Luchetti,
Neurosteroid and GABA-A receptor alterations in Alzheimer's disease, Parkinson's disease and multiple sclerosis.
2011,
Pubmed Marcade,
Etazolate, a neuroprotective drug linking GABA(A) receptor pharmacology to amyloid precursor protein processing.
2008,
Pubmed Marshall,
Early-onset Alzheimer's disease is associated with greater pathologic burden.
2007,
Pubmed McEnery,
The mitochondrial benzodiazepine receptor: evidence for association with the voltage-dependent anion channel (VDAC).
1992,
Pubmed Miledi,
Microtransplantation of functional receptors and channels from the Alzheimer's brain to frog oocytes.
2004,
Pubmed
,
Xenbase Mizukami,
GABAA receptor beta 2 and beta 3 subunits mRNA in the hippocampal formation of aged human brain with Alzheimer-related neuropathology.
1998,
Pubmed Olsen,
International Union of Pharmacology. LXX. Subtypes of gamma-aminobutyric acid(A) receptors: classification on the basis of subunit composition, pharmacology, and function. Update.
2008,
Pubmed Owen,
[3H]R05-4864 and [3H]flunitrazepam binding in kainate-lesioned rat striatum and in temporal cortex of brains from patients with senile dementia of the Alzheimer type.
1983,
Pubmed Palma,
Phosphatase inhibitors remove the run-down of gamma-aminobutyric acid type A receptors in the human epileptic brain.
2004,
Pubmed
,
Xenbase Partin,
Selective modulation of desensitization at AMPA versus kainate receptors by cyclothiazide and concanavalin A.
1993,
Pubmed
,
Xenbase Pennisi,
Motor cortex excitability in Alzheimer disease: one year follow-up study.
2002,
Pubmed Rabinovici,
Increased metabolic vulnerability in early-onset Alzheimer's disease is not related to amyloid burden.
2010,
Pubmed Rissman,
Implications for treatment: GABAA receptors in aging, Down syndrome and Alzheimer's disease.
2011,
Pubmed Roden,
Altered GABA(A) receptor subunit expression and pharmacology in human Angelman syndrome cortex.
2010,
Pubmed
,
Xenbase Russek,
Evolution of GABA(A) receptor diversity in the human genome.
1999,
Pubmed Scarf,
The translocator protein (18 kDa): central nervous system disease and drug design.
2009,
Pubmed Selkoe,
Alzheimer's disease is a synaptic failure.
2002,
Pubmed Sherwood,
Aging of the cerebral cortex differs between humans and chimpanzees.
2011,
Pubmed Thompson,
Salicylidene salicylhydrazide, a selective inhibitor of beta 1-containing GABAA receptors.
2004,
Pubmed
,
Xenbase Whiting,
Molecular and functional diversity of the expanding GABA-A receptor gene family.
1999,
Pubmed Yuan,
Statistical analysis of real-time PCR data.
2006,
Pubmed
