Neurotoxicity of quinolinic acid to spiral ganglion cells in rats.
Our study investigated the neurotoxicity of quinolinic acid (QA) to spiral ganglion cells (SGCs), observed the protective effects of N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 and magnesium ions on the QA-induced injury to SGCs, and analyzed the role of QA in otitis media with effusion (OME)-induced sensorineural hearing loss (SNHL). After culture in vitro for 72 h, SGCs were exposed to different media and divided into 4 groups: the blank control group, the QA injury group, the MK-801 treatment group, and the MgCl2 protection group. The apoptosis rate of SGCs was analyzed by Annexin V and PI double staining under the fluorescence microscopy 24 h later. SGCs were cultured in vitro for 72 h and divided into four groups: the low concentration QA group, the high concentration QA group, the MK-801 group, the MgCl2 group. The transient changes of intracellular calcium concentration were observed by the laser scanning confocal microscopy. Apoptosis rate in QA injury group was higher than that in blank control group and MgCl2 protection group (both P<0.05), but there was no significant difference between MK-801 treatment group and blank control group (P>0.05). In high concentration QA group, there was an obvious increase of the intracellular calcium concentration in SGCs, which didn't present in low concentration QA group. In MgCl2 group, the peak values of the intracellular calcium concentration in SGCs were reduced and the duration was shortened, but the intracellular calcium concentration in SGCs had no significant change in MK-801 group. It was concluded that QA could injure SGCs by excessively activating NMDA receptors on the cell membrane, which might be the mechanism by which OME induced SNHL, while Mg2+ could protect the SCGs from the neurotoxicity of QA.
Xiao
Hongjun
H
Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. xhongjunent@yahoo.com.cn
Yang
Chen
C
He
Yuanyuan
Y
Zheng
Na
N
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D016291:Dizocilpine Maleate / Q000494:pharmacology; D006319:Hearing Loss, Sensorineural / Q000139:chemically induced* / Q000209:etiology; D015636:Magnesium Chloride / Q000494:pharmacology; D010034:Otitis Media with Effusion / Q000150:complications / Q000378:metabolism*; D017378:Quinolinic Acid / Q000633:toxicity*; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013136:Spiral Ganglion / Q000166:cytology / Q000187:drug effects*
D016194:Receptors, N-Methyl-D-Aspartate; D015636:Magnesium Chloride; D016291:Dizocilpine Maleate; D017378:Quinolinic Acid; D002118:Calcium