Yu Zhi-Yuan, Wang Wei, Fritschy Jean-Marc, Witte Otto W, Redecker Christoph
Department of Neurology, Friedrich-Schiller-University, Jena, Germany.
Brain Res. 2006 Jul 12;1099(1):73-81. doi: 10.1016/j.brainres.2006.04.118. Epub 2006 Jun 15.
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.
γ-氨基丁酸A型（GABA(A)）受体是中枢神经系统中最重要的抑制性受体，在调节大脑兴奋性方面发挥着关键作用。五聚体受体通常由不同的α、β和γ亚基组成，这些亚基介导受体的功能和药理学特性，并表现出区域和时间特异性的表达模式。在不同的生理和病理生理条件下，这种多样性使得亚基组成能够发生多种适应性变化，从而导致受体具有不同的生物学和药理学特性。在此，我们研究了出生后早期、成年和老年大鼠脑中五种主要GABA(A)受体亚基（α1、α2、α3、α5、γ2）的表达情况。在出生后第10、30、60、90、180、360和540天进行免疫组织化学检测。对区域光密度的形态学和半定量评估揭示了所有亚基的特定区域和时间表达模式。该研究清楚地表明，GABA(A)受体分布的变化不仅发生在出生后早期的皮质和海马结构中，而且在青少年和老年大脑的后期也会发生。这些发现有助于更好地理解与年龄相关的大脑兴奋性变化，并进一步阐明不同GABA能药物在年轻和老年患者中的不同药理作用。
