标题：ALPHA2-ADRENERGIC RECEPTORS IN SPIRAL GANGLION NEURONS MAY MEDIATE PROTECTIVE EFFECTS OF BRIMONIDINE AND YOHIMBINE AGAINST GLUTAMATE AND HYDROGEN PEROXIDE TOXICITY
作者：J. CAI;J. LI;W. LIU
作者机构：Otolaryngology-Head and Neck Surgery, Provincial Hospital Affiliated to Shandong University, Jinan
来源：Neuroscience: An International Journal under the Editorial Direction of IBRO
关键词：a_2-adrenergic receptors;spiral ganglion neurons;brimonidine;glutamate;hydrogen peroxide;yohimbine.
摘要：Abstract-Brimonidine, an alpha_2-adrenergic receptor (a_2-AR) agonist, is thought to be neuroprotective in some types of neurons via the activation of a_2-AR. However, it is still unknown whether the a_2-ARs exist in cochlear spiral ganglion neurons (SGNs). The authors aimed to demonstrate the presence and localization of a_2-ARs in rat-cultured SGNs and to investigate the effect of brimonidine on glutamate-and hydrogen peroxide (H_2O_2)-induced damage in the primary-cultured rat SGNs. The expression of a_2-ARs was determined by reverse transcription-polymerase chain reaction, Western blot analysis and immunofluorescence. Then SGNs were exposed to glutamate or H_2O_2 respectively with or without brimonidine. Cell viability was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. Apoptosis was determined by acridine orange and Hoechst 33342/propidium iodide double staining. The protein expressions of a_2-ARs, Bax, Bcl-2, Caspase-9, Cas-pase-3, p-ERKI/2, iNOS, and artemin were determined by Western blot respectively. The cell viability was markedly reduced after exposure of glutamate (1 mM) or H_2O_2 (300 muM) to SGNs. Treatment with brimonidine protected SGNs against glutamate- or H_2O_2-induced cell damage, enhanced SGNs survival, decreased the elevation of Bax, Caspase-9, Caspase-3, p-ERK1/2, and artemin triggered by glutamate or H_2O_2, and altered the expressions of Bcl-2 and iNOS. These protective effects of brimonidine can be reversed by yohimbine.