GABA(A) receptors in aging and Alzheimer's disease.

In this article we present a comprehensive review of relevant research and reports on the GABA(A) receptor in the aged and Alzheimer's disease (AD) brain. In comparison to glutamatergic and cholinergic systems, the GABAergic system is relatively spared in AD, but the precise mechanisms underlying differential vulnerability are not well understood. Using several methods, investigations demonstrate that despite resistance of the GABAergic system to neurodegeneration, particular subunits of the GABA(A) receptor are altered with age and AD, which can induce compensatory increases in GABA(A) receptor subunits within surrounding cells.

Olivo-cortico-nuclear localizations within crus I of the cerebellum.

Retrograde and anterograde tracers were microinjected into the folia of crus I of the cat cerebellum to investigate spatial localization in olivo-cerebellar and cortico-nuclear projections. The folia were shown to be mainly occupied in rostrocaudal succession by three zones receiving their olivo-cerebellar climbing fiber afferents from parts of, respectively, the dorsal lamella of the principal olive, the ventral lamella of the principal olive, and the rostral half of the medial accessory olive. These zones are presumably parts of the D(2), D(1), and C(2) cerebellar cortical zones, as earlier proposed by Rosina and Provini ([1982] Neuroscience 7:2657-2676).

Age-related alterations in GABA(A) receptor subunits in the nonhuman primate hippocampus.

Pharmacological studies have documented that altered drug responses, particularly to benzodiazepines, are common in elderly populations. While numerous factors may contribute to changes in drug response, age-related alterations in the molecular composition of GABA(A) receptors may be a key factor in regulating these responses. We employed quantitative densitometry to examine the cytological features and density of highly prevalent hippocampal GABA(A) receptor subunits (alpha1 and beta2/3) in young and aged rhesus monkeys.

Subregional analysis of GABA(A) receptor subunit mRNAs in the hippocampus of older persons with and without cognitive impairment.

We employed in situ hybridization and quantitative densitometry techniques to examine hippocampal mRNA expression of GABA(A) receptor subunits alpha1 and alpha5 in human subjects with progressing cognitive impairment. Included in this study were 17 participants of the Religious Order Study (ROS), who were categorized into three groups based upon degree of cognitive impairment: no cognitive impairment (n = 6); moderate cognitive impairment (n = 5); and probable Alzheimer's disease (AD) (n = 6). While the levels of each specific subunit mRNA were relatively homogeneously distributed throughout the five hippocampal subregions analyzed (CA1-4, and the granule cell layer of the dentate gyrus), mRNA expression of the alpha1 receptor subunit was found to be 20% reduced in the moderate cognitive impairment group as compared to the no cognitive impairment group.

Differential preservation of AMPA receptor subunits in the hippocampi of Alzheimer's disease patients according to Braak stage.

The Alzheimer's disease (AD) brain, characterized pathologically by the presence of senile plaques and neurofibrillary tangles, contains regions that are differentially prone toward development of AD pathology. Within these "vulnerable" regions, specific cell populations appear to be selectively affected; the pyramidal cells of the hippocampal subiculum subfield constitute such a vulnerable region. This study investigated whether the AMPA receptor subunit content (GluR1, GluR2, GluR2/3) within "vulnerable" vs.

Biochemical and molecular studies of NMDA receptor subunits NR1/2A/2B in hippocampal subregions throughout progression of Alzheimer's disease pathology.

Alzheimer's disease (AD) is characterized by loss of specific cell populations within selective subregions of the hippocampus. Excitotoxicity, mediated via ionotropic glutamate receptors, may play a crucial role in this selective neuronal vulnerability. We investigated whether alterations in NMDA receptor subunits occurred during AD progression.

Alterations in hippocampal voltage-gated calcium channel alpha 1 subunit expression patterns after kainate-induced status epilepticus in aging rats.

Young adult and aged male Fisher 344 rats underwent kainate-induced convulsive status epilepticus (SE) for 4 h prior to sacrifice to determine potential aging-related differences in the effect of prolonged SE on the expression of hippocampal voltage-gated calcium channels (VGCCs). Immunohistochemistry was performed on hippocampal sections using antibodies directed against the alpha1 subunit of class A-D VGCCs. Compared to age-matched controls, SE animals showed a marked loss of alpha1A immunoreactivity (IR) in CA3 and the hilus, which was more prominent in aged animals.

Plasticity of glutamate and GABAA receptors in the hippocampus of patients with Alzheimer's disease.

Aim: In Alzheimer's disease (AD) it is well known that specific regions of the brain are particularly vulnerable to the pathologic insults of the disease. In particular, the hippocampus is affected very early in the disease and by end stage AD is ravaged by neurofibrillary tangles and senile plaques (i.e.