Department of Neurology, Friedrich Schiller University, Erlanger Allee 101, 07747 Jena, Germany.
Neurobiol Aging. 2010 Mar;31(3):504-11. doi: 10.1016/j.neurobiolaging.2008.04.006. Epub 2008 May 19.
Recent studies with functional magnetic brain imaging showed different task-related patterns of brain activation and deactivation in aged as compared to young healthy subjects. We hypothesized that these changes of brain activation patterns might be due to age-dependent changes of neuronal excitability. Therefore, we experimentally studied the functional cortical inhibition by paired pulse stimulation in brain slices of young adult (3 months), aged adult (24 months) and old (36 months) male rats. Field potentials were evoked by application of double pulses at layer VI/white matter and recorded in layer II/III. We also analyzed the regional distribution of five major gamma-aminobutyric acid A (GABA(A)) receptor subunits (alpha1, alpha2, alpha3, alpha5, and gamma2) by immunohistochemistry. A reduced functional inhibition in aged as compared to young animals associated with an altered composition of GABA(A)-receptors, especially a reduction of subunit alpha5 in aged animals, was shown. The present study suggests that the age-dependent functional activation patterns and possibly also the cognitive and motor abilities are at least partially modulated by an age-dependent alteration of functional inhibition in the neocortex.
最近的功能磁共振脑成像研究表明，与年轻健康受试者相比，老年受试者在执行任务时大脑的激活和失活模式存在差异。我们假设这些大脑激活模式的变化可能是由于神经元兴奋性的年龄依赖性变化所致。因此，我们在年轻成年（3 个月）、老年成年（24 个月）和老年（36 个月）雄性大鼠的脑切片中，通过双脉冲刺激实验研究了功能皮质抑制。通过在第 VI 层/白质施加双脉冲来诱发场电位，并在第 II/III 层记录。我们还通过免疫组织化学分析了五种主要的γ-氨基丁酸 A（GABA(A)）受体亚基（alpha1、alpha2、alpha3、alpha5 和 gamma2）的区域分布。与年轻动物相比，老年动物的功能抑制作用降低，与 GABA(A)受体组成的改变有关，特别是老年动物的亚基 alpha5 减少。本研究表明，年龄相关的功能激活模式，以及认知和运动能力，至少部分受到新皮质功能抑制的年龄依赖性改变的调节。
