Changes in neocortical and hippocampal GABAA receptor subunit distribution during brain maturation and aging.
gamma-Aminobutyric acid type A (GABA(A)) receptors are the most important inhibitory receptors in the central nervous system, playing a pivotal role in the regulation of brain excitability. The pentameric receptor is commonly composed of different alpha, beta, and gamma subunits which mediate the function and pharmacology of the receptor and show regional- and temporal-specific expression patterns. Under varying physiological and pathophysiological conditions, this diversity allows a multitude of adaptive changes in subunit composition leading to distinct biological and pharmacological properties of the receptor. Here, we investigated the expression of five major GABA(A) receptors subunits (alpha1, alpha2, alpha3, alpha5, gamma2) in early postnatal, adult, and aged rat brains. Immunohistochemistry was performed at postnatal day 10, 30, 60, 90, 180, 360, and 540. Morphological and semi-quantitative evaluations of regional optical densities revealed specific regional and temporal expression patterns for all subunits. The study clearly demonstrated that changes in GABA(A) receptor distribution not only occur in the early postnatal cortex and hippocampal formation but also during later periods in the adolescent and aging brain. These findings contribute to a better understanding of age-related changes in brain excitability and further elucidate the distinct pharmacological effects of different GABAergic drugs in young and elderly patients.
Yu
Zhi-Yuan
ZY
Department of Neurology, Friedrich-Schiller-University, Jena, Germany.
Wang
Wei
W
Fritschy
Jean-Marc
JM
Witte
Otto W
OW
Redecker
Christoph
C
D000367:Age Factors; D000375:Aging / Q000502:physiology*; D000818:Animals; D006624:Hippocampus / Q000254:growth & development / Q000378:metabolism*; D007150:Immunohistochemistry / Q000379:methods; D019579:Neocortex / Q000254:growth & development / Q000378:metabolism*; D021122:Protein Subunits / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000378:metabolism*
D021122:Protein Subunits; D011963:Receptors, GABA-A