Limatola Cristina, Lauro Clotilde, Catalano Myriam, Ciotti Maria Teresa, Bertollini Cristina, Di Angelantonio Silvia, Ragozzino Davide, Eusebi Fabrizio
Istituto Pasteur-Fondazione Cenci Bolognetti and Dipartimento di Fisiologia Umana e Farmacologia, Centro di Eccellenza BEMM, Università di Roma La Sapienza, P.le A. Moro 5, I00185 Rome, Italy.
J Neuroimmunol. 2005 Sep;166(1-2):19-28. doi: 10.1016/j.jneuroim.2005.03.023.
Excitotoxicity is a cell death caused by excessive exposure to glutamate (Glu), contributing to neuronal degeneration in many acute and chronic CNS diseases. We explored the role of fractalkine/CX3CL1 on survival of hippocampal neurons exposed to excitotoxic doses of Glu. We found that: CX3CL1 reduces excitotoxicity when co-applied with Glu, through the activation of the ERK1/2 and PI3K/Akt pathways, or administered up to 8 h after Glu insult; CX3CL1 reduces the Glu-activated whole-cell current through mechanisms dependent on intracellular Ca2+; CX3CL1 is released from hippocampal cells after excitotoxic insult, likely providing an endogenous protective mechanism against excitotoxic cell death.
兴奋性毒性是一种因过度暴露于谷氨酸（Glu）而导致的细胞死亡，在许多急性和慢性中枢神经系统疾病中会促使神经元退化。我们探究了趋化因子/CX3CL1在暴露于兴奋性毒性剂量Glu的海马神经元存活中的作用。我们发现：当与Glu共同应用时，CX3CL1通过激活ERK1/2和PI3K/Akt通路来降低兴奋性毒性，或者在Glu损伤后长达8小时给药也可降低兴奋性毒性；CX3CL1通过依赖细胞内Ca2+的机制降低Glu激活的全细胞电流；兴奋性毒性损伤后CX3CL1从海马细胞中释放，这可能提供了一种针对兴奋性毒性细胞死亡的内源性保护机制。
