Involvement of the Snk-SPAR pathway in glutamate-induced excitotoxicity in cultured hippocampal neurons.
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.
Wu
Lan-Xiang
LX
Institute for Brain Disorders, Dalian Medical University, 465 Zhong Shan Road, Shahekou District, Dalian 116027, China.
Sun
Chang-Kai
CK
Zhang
Yu-Mei
YM
Fan
Ming
M
Xu
Jing
J
Ma
Hui
H
Zhang
Jian
J
D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D049229:Dendritic Spines / Q000187:drug effects; D000076122:Disks Large Homolog 4 Protein; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D020690:GTPase-Activating Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D018698:Glutamic Acid / Q000494:pharmacology*; D006624:Hippocampus / Q000166:cytology*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D008954:Models, Biological; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D011494:Protein Kinases / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects*; D013997:Time Factors
D000076122:Disks Large Homolog 4 Protein; C501449:Dlg4 protein, rat; D018691:Excitatory Amino Acid Antagonists; D020690:GTPase-Activating Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C479629:Sipa1l1 protein, rat; D018698:Glutamic Acid; D016291:Dizocilpine Maleate; D007770:L-Lactate Dehydrogenase; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; C444640:serum-inducible kinase