Departamento de Biología Celular y Molecular, CUCBA, Universidad de Guadalajara, Zapopan, Jalisco, Mexico.
Neurosci Lett. 2013 Sep 27;552:52-7. doi: 10.1016/j.neulet.2013.07.038. Epub 2013 Aug 6.
Seizure susceptibility appears to be greater in males than females during the early developmental stages of the brain when the gamma-aminobutyric acid (GABA), acting through its GABA-A receptor, predominantly produces neuronal depolarization. GABA-mediated excitation has been observed when the NKCC1 (chloride importer) expression level is higher than KCC2 (chloride exporter). In this study, the relative protein expression of NKCC1 and KCC2 over β-actin was evaluated in the hippocampus and entorhinal cortex of male and female rats during postnatal days (PND) 1, 3, 5, 7, 9, 11, 13 and 15 using Western blotting assays. For both cerebral regions in the females, the NKCC1/β-actin expression ratio was constant during all evaluated ages, whereas the KCC2/β-actin expression ratio increased gradually until reaching a maximal level at PND9 that was nearly three- and ten-fold higher in the hippocampus and entorhinal cortex, respectively, compared with the initial level. In males, the NKCC1/β-actin expression ratio was constant during the first week, peaking almost three-fold higher than the initial level at PND9 in the hippocampus and at PND11 in the entorhinal cortex and then returning to the initial values at PND13, whereas the KCC2/β-actin expression ratio increased gradually to reach a maximal and steady level at PND5, which were nearly two- and four-fold higher in the hippocampus and entorhinal cortex, respectively, compared with the intial level. In conclusion, the NKCC1/β-actin and KCC2/β-actin expression ratios displayed a specific expression profile for each gender and cerebral region, which could be related with the differences in seizure susceptibility observed between genders.
在大脑发育的早期阶段，γ-氨基丁酸（GABA）通过其 GABA-A 受体作用，主要产生神经元去极化，此时男性的癫痫易感性似乎高于女性。当 NKCC1（氯离子内流体）的表达水平高于 KCC2（氯离子外排体）时，会观察到 GABA 介导的兴奋。在本研究中，通过 Western blot 分析评估了雄性和雌性大鼠在出生后第 1、3、5、7、9、11、13 和 15 天（PND）的海马体和内嗅皮层中 NKCC1 和 KCC2 相对于 β-肌动蛋白的相对蛋白表达。对于女性的两个大脑区域，NKCC1/β-肌动蛋白表达比值在所有评估年龄期间保持恒定，而 KCC2/β-肌动蛋白表达比值逐渐增加，直到在 PND9 达到最大值，与初始水平相比，在海马体和内嗅皮层中分别增加了近三倍和十倍。在雄性中，NKCC1/β-肌动蛋白表达比值在第一周内保持恒定，在 PND9 时在海马体中达到初始水平的近三倍，在内嗅皮层中达到 PND11 时达到峰值，然后在 PND13 时恢复到初始值，而 KCC2/β-肌动蛋白表达比值逐渐增加，在 PND5 时达到最大值和稳定水平，与初始水平相比，在海马体和内嗅皮层中分别增加了近两倍和四倍。总之，NKCC1/β-肌动蛋白和 KCC2/β-肌动蛋白表达比值在每个性别和大脑区域表现出特定的表达模式，这可能与两性之间观察到的癫痫易感性差异有关。
