Increased Susceptibility to Ischemic Brain Injury in Neuroplastin 65-Deficient Mice Likely via Glutamate Excitotoxicity.
Increased Susceptibility to Ischemic Brain Injury in Neuroplastin 65-Deficient Mice Likely via Glutamate Excitotoxicity.
复制标题
神经塑蛋白 65 缺陷小鼠对缺血性脑损伤的易感性增加，可能是通过谷氨酸兴奋毒性所致
DOI：
10.3389/fncel.2017.00110
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发表时间：
2017
影响因子：
5.3
通讯作者：
Yuan Q
中科院分区：
文献类型：
--
作者：
Hu Y;Zhan Q;Zhang H;Liu X;Huang L;Li H;Yuan Q
细胞粘附分子（CAM）参与成年脑中突触可塑性和神经元存活。神经致活蛋白65（Neuroplastin 65，Np 65）是CAMs免疫球蛋白超家族的成员之一，具有脑特异性，在啮齿类动物前脑中高度表达。Np 65在突触可塑性中的作用已被证实，然而，Np 65是否影响神经元的存活仍然未知。为了解决这个缺口，据我们所知，我们产生了第一个Np 65敲除（KO）小鼠。通过阻塞大脑中动脉来进行缺血性中风模型，我们显示与野生型（WT）小鼠相比，Np 65 KO小鼠表现出更严重的神经功能缺损和更大的梗死体积（通过TTC染色测量），以及更多的凋亡细胞（通过TUNEL染色证实）。此外，蛋白质印迹分析显示，与WT小鼠相比，Np 65 KO小鼠的囊泡谷氨酸转运蛋白1（VGluT 1）和N-甲基D-天冬氨酸受体（包括NR 1、NR 2A和NR 2B）显著增加。相比之下，囊泡γ-氨基丁酸转运蛋白（VGAT）水平在两种基因型中风后没有变化。此外，与WT小鼠相比，中风后Np 65 KO小鼠的磷酸化细胞外信号调节激酶1/2水平显著升高。总之，这些结果表明，Np 65 KO小鼠可能更容易发生脑缺血事件。
Cell adhesion molecules (CAMs) are involved in synaptic plasticity and neuronal survival in the adult brain. Neuroplastin 65 (Np65), one member of the immunoglobulin superfamily of CAMs, is brain-specific and highly expressed in rodent forebrain. The roles of Np65 in synaptic plasticity have been confirmed, however, whether Np65 affects neuronal survival remains unknown. To address this gap, we generated, to our knowledge, the first Np65 knockout (KO) mice. By occluding middle cerebral artery to perform ischemic stroke model, we showed that Np65 KO mice exhibited more severe neurological deficits and larger infarction volume measured by TTC staining and more apoptotic cells confirmed by TUNEL staining compared to wild type (WT) mice. Besides, western blot analysis showed that the vesicular glutamate transporter-1(VGluT1), and N-Methyl D-Aspartate receptors, including NR1, NR2A, and NR2B were significantly increased in Np65 KO mice compared with WT mice. In contrast, vesicular gamma amino butyric acid transporter (VGAT) levels were unchanged in two genotypes after stroke. Additionally, phosphorylated-extracellular signal-regulated kinase 1/2 levels were significantly increased in Np65 KO mice compared with WT mice after stroke. Together, these results suggest that Np65 KO mice may be more susceptible to ischemic events in the brain.