Center for Neuroscience, University of Pittsburgh, Pittsburgh, PA, USA.
Department of Neurological Surgery, University of Pittsburgh Medical Center, 4401 Penn Ave, Pittsburgh, PA, 15224, USA.
Mol Neurobiol. 2024 Sep;61(9):7256-7268. doi: 10.1007/s12035-024-04043-5. Epub 2024 Feb 20.
Extensive effort has been made to study the role of synaptic deficits in cognitive impairment after traumatic brain injury (TBI). Neurogranin (Ng) is a calcium-sensitive calmodulin (CaM)-binding protein essential for Ca/CaM-dependent kinase II (CaMKII) autophosphorylation which subsequently modulates synaptic plasticity. Given the loss of Ng expression after injury, additional research is warranted to discern changes in hippocampal post-synaptic signaling after TBI. Under isoflurane anesthesia, adult, male and female Sprague-Dawley rats received a sham/control or controlled cortical impact (CCI) injury. Ipsilateral hippocampal synaptosomes were isolated at 24 h and 1, 2, and 4 weeks post-injury, and western blot was used to evaluate protein expression of Ng-associated signaling proteins. Non-parametric Mann-Whitney tests were used to determine significance of injury for each sex at each time point. There were significant changes in the hippocampal synaptic expression of Ng and associated synaptic proteins such as phosphorylated Ng, CaMKII, and CaM up to 4 weeks post-CCI, demonstrating TBI alters hippocampal post-synaptic signaling. This study furthers our understanding of mechanisms of cognitive dysfunction within the synapse sub-acutely after TBI.
研究人员在很大程度上研究了突触缺陷在创伤性脑损伤（TBI）后认知障碍中的作用。神经颗粒蛋白（Ng）是一种钙敏感受体钙调蛋白（CaM）结合蛋白，对 Ca/CaM 依赖性激酶 II（CaMKII）的自磷酸化至关重要，而 CaMKII 的自磷酸化又调节突触可塑性。鉴于损伤后 Ng 表达的丧失，有必要进行更多的研究来辨别 TBI 后海马突触后信号的变化。在异氟烷麻醉下，成年雄性和雌性 Sprague-Dawley 大鼠接受假手术/对照或皮质控制冲击（CCI）损伤。在损伤后 24 小时和 1、2 和 4 周时分离同侧海马突触体，并通过 Western blot 评估 Ng 相关信号蛋白的蛋白表达。非参数曼-惠特尼检验用于确定每个性别在每个时间点的损伤显著性。在 CCI 后长达 4 周，海马突触中的 Ng 和相关突触蛋白（如磷酸化 Ng、CaMKII 和 CaM）的表达发生了显著变化，这表明 TBI 改变了海马突触后信号。这项研究进一步加深了我们对 TBI 后突触亚急性认知功能障碍机制的理解。
