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Involvement of the Snk-SPAR pathway in glutamate-induced excitotoxicity in cultured hippocampal neurons

2007; Elsevier BV; Volume: 1168; Linguagem: Inglês

10.1016/j.brainres.2007.06.082

1872-6240

Lanxiang Wu, Changkai Sun, Yumei Zhang, Ming Fan, Jing Xu, Hui Ma, Zhang Jian,

Ion channel regulation and function

The serum-induced kinase (Snk)-spine-associated Rap GTPase-activating protein (SPAR) signaling pathway is reported as a new molecular mechanism in activity-dependent remodeling of synapses. However, the relationship between Snk-SPAR pathway and glutamate-induced excitotoxicity is not well understood. We report here that in cultured hippocampal neurons, glutamate stimulation induces the activation of Snk-SPAR pathway, and leads to a loss of mature dendritic spines. The time-dependent changes in Snk and SPAR expression after glutamate exposure are also elucidated. Furthermore, the activation of Snk-SPAR pathway induced by glutamate treatment can be blocked by an NMDA receptor antagonist, MK801. These results demonstrate that Snk-SPAR pathway may play a pivotal role in glutamate-induced excitotoxic damage in CNS through regulating the stability of synapse.