ABSTRACT
Objective To study the effect of mAbN1,a monoclonal antibody against N-methyl-D-aspartate receptor subunit 1(NR1)on Ca2+ influx after glutamate stimulation in cultured rat hippocampal neurons.Methods Excitotoxicity was induced by glutamate in cultured hippocampal neurons.Confocal laser scanning microscopy was used to observe the changes in intracellular free calcium concentration([Ca2+]i)at the level of cultured hippocampal neurons following pretreatment with mAbN1 and MK-801.Intracellular free calcium was imaged after loading cells with the fluorescent dye indicator fluo-3/AM.Results Our findings indicate that as compared with MK-801,mAbN1 can more significantly attenuate the glutamate-induced [Ca2+]i increase,and it has no effect on [Ca2+]i in physiological condition.Conclusion mAbN1 may alter the secondary structure of NR,consequently influence Ca2+ influx in excitotoxicity process.
ABSTRACT
Tissue plasminogen activator(tPA) had been used clinically as a choice drug for the therapy of ischemic shock.Evidence in animal experiments suggests that tPA may play a neurotoxic role in central nervous system(CNS) via the induction of microglial activation,degradation of laminin matrix and enhancement of the N-methyl-D-aspartate(NMDA) receptor-mediated signaling in neurons,other reports imply tPA could protect rat neuronal cells from zinc-induced toxicity.