Department of Neurochemistry, Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Leontovich Str. 9, Kyiv 01601, Ukraine.
Neurosci Lett. 2012 Aug 30;524(2):69-73. doi: 10.1016/j.neulet.2012.07.015. Epub 2012 Jul 25.
Hypoxia-evoked seizures (H/S) early in life lead to multiple chronic neurological deficits. Here, we present the results of studying GABA release and uptake in hippocampal axon terminals of rats exposed to H/S at 10-12 days of age. We characterized (i) exocytotic release of GABA; (ii) the initial rate of GABA uptake; (iii) the regulation of GABA release by presynaptic GABA(B) receptors. Rats were used for experiments 2, 4 and 8 weeks after H/S. We found that exocytotic [(3)H]GABA release was higher in rats exposed to H/S, and a maximal difference in the release was observed between the control and experimental rats tested 2 weeks after H/S. In contrast, the initial rate of GABA uptake decreased with age, and this tendency was more pronounced in rats exposed to H/S. Using (±)-baclofen and SKF 97541 as agonists of GABA(B) receptor, we revealed that a significant difference in the auto-inhibition of exocytotic [(3)H]GABA release was detected only between the control and experimental adult rats (8 weeks after hypoxia). The inhibitory effect dropped dramatically in the control adults, but only slightly decreased in adult rats exposed to H/S, thus becoming threefold more potent after hypoxic injury. Together, the results show that H/S affects the dynamics of age-dependent changes in the GABAergic system, and that the enhanced GABA(B) receptor-mediated auto-inhibition can be an important factor in weakening the postsynaptic inhibition and in the development of hyperexcitability in rats exposed to H/S.
缺氧诱导的癫痫发作（H/S）在生命早期发生，导致多种慢性神经功能缺损。在这里，我们介绍了在 10-12 天大的大鼠中暴露于 H/S 后研究海马轴突末梢 GABA 释放和摄取的结果。我们描述了：（i）GABA 的胞吐释放；（ii）GABA 摄取的初始速率；（iii）GABA 释放的突触前 GABA(B) 受体调节。H/S 后 2、4 和 8 周，大鼠用于实验。我们发现暴露于 H/S 的大鼠中胞吐性[3H]GABA 释放更高，并且在 H/S 后 2 周测试的对照和实验大鼠之间观察到最大差异。相比之下，GABA 摄取的初始速率随年龄而降低，而这种趋势在暴露于 H/S 的大鼠中更为明显。使用（±）-baclofen 和 SKF 97541 作为 GABA(B) 受体激动剂，我们发现仅在对照和成年实验大鼠（H/S 后 8 周）之间检测到胞吐性[3H]GABA 释放的自动抑制存在显著差异。在对照成年人中，抑制作用急剧下降，但在暴露于 H/S 的成年大鼠中仅略有下降，因此在缺氧损伤后变得更有效三倍。总之，这些结果表明 H/S 影响 GABA 能系统随年龄变化的动力学，并且增强的 GABA(B) 受体介导的自动抑制可能是减弱突触后抑制和在 H/S 暴露的大鼠中易化兴奋性的重要因素。
