Department of Biomedical Sciences, University of Prince Edward Island, Charlottetown, PE, Canada.
Brain Res. 2010 May 17;1331:114-23. doi: 10.1016/j.brainres.2010.03.054. Epub 2010 Mar 21.
In the rat, early postnatal development is a critical period for neuronal migration, differentiation and network formation, requiring appropriate and timely glutamate and gamma-aminobutyric acid (GABA) signaling. Insults that affect either of these systems may result in increased excitatory activity, potentially leading to changes in neuronal proliferation and/or connectivity. We have previously shown that postnatal administration of low doses of domoic acid (DOM) can produce many of the behavioral and morphological changes found in current animal models of temporal lobe epilepsy (TLE), as well as the human condition. Using immunohistochemical techniques, we sought to characterize alterations in specific hippocampal GABAergic subpopulations at various locations along the septo-temporal axis in the DOM model. Results show decreased levels of the GABA-synthesizing enzyme glutamic acid decarboxylase (GAD) in the ventral hilus and region- and sex-specific reductions in parvalbumin (PV)-containing immunoreactivity, but no alterations in somatostatin (SST) expression. These regional and sex-dependent changes in specific subpopulations of GABAergic interneurons may contribute to seizure development in this slowly progressing developmental model of TLE, and highlight how even subtle intervention may alter the interplay between glutamate and GABA systems during critical developmental stages.
在大鼠中，早期产后发育是神经元迁移、分化和网络形成的关键时期，需要适当和及时的谷氨酸和γ-氨基丁酸（GABA）信号。影响这些系统中任何一个系统的损伤都可能导致兴奋性活动增加，从而导致神经元增殖和/或连接的变化。我们之前已经表明，产后给予低剂量的脱氢乙酸（DOM）可以产生许多当前颞叶癫痫（TLE）动物模型以及人类疾病中发现的行为和形态变化。我们使用免疫组织化学技术，试图在 DOM 模型中沿隔颞轴的各个位置描述特定海马 GABA 能亚群的变化。结果显示，腹侧门齿和区域和性别特异性的谷氨酸脱羧酶（GAD）合成酶减少，含有 GABA 能的免疫反应减少，但生长抑素（SST）表达没有改变。这些特定 GABA 能中间神经元亚群的区域性和性别依赖性变化可能有助于癫痫发作的发展，这种缓慢进展的 TLE 发育模型强调了即使是轻微的干预也可能改变关键发育阶段谷氨酸和 GABA 系统之间的相互作用。
