Early down regulation of the glial Kir4.1 and GLT-1 expression in pericontusional cortex of the old male mice subjected to traumatic brain injury
Early down regulation of the glial Kir4.1 and GLT-1 expression in pericontusional cortex of the old male mice subjected to traumatic brain injury
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DOI：
10.1007/s10522-013-9459-y
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发表时间：
2013-10-01
期刊：
影响因子：
4.5
通讯作者：
Prasad, S.
中科院分区：
文献类型：
--
作者：
Gupta, R. K.;Prasad, S.
星形胶质细胞通过向神经元提供基质、分泌神经营养因子、维持K+和谷氨酸稳态从而控制在衰老过程中经历改变的突触可塑性而在脑功能中发挥多种作用。K+和谷氨酸稳态分别由突触中的星形胶质细胞膜结合内向整流K+通道（Kir4.1）和谷氨酸转运蛋白-1（GLT-1或EAAT-2）蛋白维持，并且它们的表达可能由于创伤性脑损伤（TBI）而改变。此外，还不清楚这种变化是否与年龄有关。为了发现这一点，在成年和老年雄性AKR品系小鼠实验性诱导TBI使用CHI技术，和Kir4.1和GLT-1的表达在不同的时间间隔在周围皮质中的Western印迹和半定量RT-PCR技术进行了研究。在这里，我们报告Kir4.1和GLT-1基因在转录和蛋白质水平的表达显着下调，在老年TBI小鼠的同侧皮质周围相比，在成年TBI小鼠作为损伤后的时间的函数。此外，这两种基因的表达在老年小鼠中很早就开始下降，即，与成年TBI小鼠中从第四小时开始的相比，TBI后第一小时开始。因此，TBI以年龄和时间依赖性方式影响Kir4.1和GLT-1基因的表达，并且与成年小鼠相比，它可能导致老年小鼠突触早期更多的K+和谷氨酸的积累。这可能与TBI诱导的老年早期和严重的神经元去极化和兴奋性神经毒性有关。
Astroglia play multiple roles in brain function by providing matrix to neurons, secreting neurotrophic factors, maintaining K+ and glutamate homeostasis and thereby controlling synaptic plasticity which undergoes alterations during aging. K+ and glutamate homeostasis is maintained by astrocytes membrane bound inwardly rectifying K+ channel (Kir4.1) and glutamate transporter-1 (GLT-1 or EAAT-2) proteins, respectively in the synapse and their expression may be altered due to traumatic brain injury (TBI). Also, it is not well understood whether this change is age dependent. To find out this, TBI was experimentally induced in adult and old male AKR strain mice using CHI technique, and expression of the Kir4.1 and GLT-1 in the pericontusional cortex at various time intervals was studied by Western blotting and semi quantitative RT-PCR techniques. Here, we report that expression of both Kir4.1 and GLT-1 genes at transcript and protein levels is significantly down regulated in the pericontusional ipsi-lateral cortex of old TBI mice as compared to that in the adult TBI mice as function of time after injury. Further, expression of both the genes starts decreasing early in old mice i.e., from the first hour after TBI as compared to that starts from fourth hour in adult TBI mice. Thus TBI affects expression of Kir4.1 and GLT-1 genes in age- and time dependent manner and it may lead to accumulations of more K+ and glutamate early in the synapse of old mice as compared to adult. This may be implicated in the TBI induced early and severe neuronal depolarization and excito-neurotoxicity in old age.