Expression of the prodynorphin gene after experimental brain injury and its role in behavioral dysfunction
Expression of the prodynorphin gene after experimental brain injury and its role in behavioral dysfunction
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DOI：
10.1177/153537020322800304
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发表时间：
2003-03-01
影响因子：
3.2
通讯作者：
Dash, PK
中科院分区：
文献类型：
--
作者：
Redell, JB;Moore, AN;Dash, PK
创伤性脑损伤(TBI)会导致谷氨酸等神经递质的过度释放，并增加细胞内钙水平。脑外伤引起的钙水平升高，也许还有其他细胞内第二信使，都会改变许多基因的表达。其中一些基因的蛋白质产物可能是脑损伤相关记忆障碍的信号。因此，鉴定脑损伤后海马区表达改变的基因，并阐明其蛋白产物的作用(S)，可能有助于阐明脑挫伤后记忆障碍的分子机制。海马区是内侧颞叶的一个结构，在记忆形成和存储中发挥关键作用。前强啡肽基因在海马颗粒细胞中表达，据报道，由于细胞内钙升高，其表达增强。强啡肽原蛋白被蛋白水解酶降解，产生多种强啡肽，通过激活突触前kappa阿片受体来调节神经递质的释放。在本研究中，我们报道：1)脑损伤后大鼠海马区前强啡肽基因表达增加，2)脑挫伤后24小时强啡肽免疫反应增强，3)脑室注射K受体拮抗剂去甲肾上腺素(Nor-BNI)会损害大鼠随后的空间记忆能力。这些结果提示强啡肽在脑创伤后可能起到有益的作用。
Traumatic brain injury (TBI) causes excess release of neurotransmitters, such as glutamate, and increases intracellular calcium levels. Elevated levels of calcium, and perhaps other intracellular second messengers, as a result of TBI can alter the expression of many genes. The protein products of some of these genes may be signals for TBI-associated memory dysfunction. Therefore, identification of genes whose expression is altered after TBI in the hippocampus, a structure in the medial temporal lobe that plays a critical role in memory formation and storage, and elucidation of the role(s) of their protein products may shed light on the molecular mechanisms underlying TBI-elicited memory dysfunction. The prodynorphin gene is expressed in hippocampal granule cells, and its expression has been reported to be enhanced as a result of elevated intracellular calcium. The prodynorphin protein is proteolytically cleaved to generate multiple dynorphin peptides, which can modulate neurotransmitter release through the activation of presynaptic kappa opioid receptors. In this study, we report that 1) TBI transiently increases prodynorphin mRNA in the hippocampus, 2) dynorphin peptide immunoreactivity is enhanced for up to 24 hr after TBI and 3) intracerebroventricular infusion of the K receptor antagonist nor-binaltorphimine (nor-BNI) impairs subsequent performance in a spatial memory task. These results suggest that dynorphin action may serve a beneficial role after TBI.