Summary
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.
Similar content being viewed by others
References
Mutlu C, Odabasi AO, Metin K, et al. Sensorineural hearing loss associated with otitis media with effusion in children. Int J Pediat Otorhinolaryngol, 1998,46(3): 179–184
Yang C, Xiao HJ. Otitis media with effusion and sensorineural hearing loss. Int J Otolaryngol Head Neck Surg (Chinese), 2007,31(6):354–356
Ryding M, konradsson K, White P, et al. Hearing loss after “refractory” secretory otitis media. Acta Oto-Laryngologica, 2005,125(3):250–255
Ghaheri BA, Kempton JB, Pillers DA, et al. Cochlear cytokine gene expression in murine acute otitis media. Laryngoscope, 2007,117(1):22–29
Park CW, Han JH, Jeong JH, et al. Detection rates of bacteria in chronic otitis media with effusion in children. Korean Med Sci, 2004,19(5):735–738
Takumidal M, Anniko M. Localization of endotoxin in the inner ear following inoculation into the middle ear. Acta Otolaryngol, 2004,124(7):772–777
Beurg M, Hafidi A, Skinner L, et al. The mechanism of pneumolysin-induced cochlear hair cell death in the rat. J Physiolo, 2005,568(1):211–227
Engel F, Blatz R, Schliebs R, et al. Bacterial cytolysin perturbs round window membrane permeability barrier in vivo: possible cause of sensorineural hearing loss in acute otitis media. Infect Immun, 1998,66(1):343–346
Lu HT, Gong SS. Anatomic structure, physiological function and clinical meaning. Guo Wai Yi Xue Er Bi Hou Xue Fen Ce (Chinese), 2002,26(4):204–217
Yellon RF, Rose E, Kenna MA, et al. Sensorineural hearing loss from quinolinic acid: a neurotoxin in middle ear effusions. Laryngoscope, 1994,104(2):176–181
Ribeiro CA, Grando V, Dutra Filho CS, et al. Evidence that quinolinic acid severely impairs energy metabolism through activation of NMDA receptors in striatum from developing rats. J Neurochem, 2006, 99(6):1531–1542
Matyja E. Intracellular calcium overload in a model of quinolinic acid neurotoxicity in organotypic culture of rat hippocampus, inhibited by nimodipine. Folia Neuropathol, 1997,35(1):8–17
Whitlon DS, Ketels KV, Coulson MT. Survival and morphology neurons in dissociated cultures of newborn mouse spiral ganglion. Neuroscience, 2006, 138(2):653–662
Steinbach S, Lutz J. Glutamate induces apoptosis in cultured spiral ganglion explants. Biochem Biophys Res Commun, 2007,357(1):14–19
Estrada Sánchez AM, Mejía-Toiber J, Massieu L, et al. Excitotoxic neuronal death and the pathogenesis of Huntington’s disease. Arch Med Res, 2008,39(3): 265–276
Bordelon YM, Chesselet MF, Erecińska M, et al. Effects of intrastriatal injection of quinolinic acid on electrical activity and extracellular ion concentrations in rat striatum in vivo. Neuroscience, 1998,83(2): 459–469
Zhou Q, Wang ZM. Studies on neurotoxic effects of quinolinic acid on spiral ganglion. Shanghai Med J (Chinese), 1999,22(5):286–288
Jiang M, Sun H, Zhang YQ, et al. Excitotoxic effect of glutamate on the afferent neurons in guinea pigs. Zhongnan Da Xue Xue Bao (Chinese), 2004,29(2): 170–173
Luccini E, Musante V, Neri E, et al. N-methyl-D-aspartate auroreceptors respond to low and high agonist concentrations by facilitating, respectively, exocytosis and carrier-mediated release of glutamate in rat hippocampus. J Neurosci Res, 2007,85(16):3657–3665
Qi BM, Wang JB. Distribution of glu in the rat inner ear and its significance. J Audiol Speech Pathol (Chinese), 2004,12(1):53–55
Han TZ, Li YH. Structure and pharmacology properties of NMDA receptor. Adv Psychol Sci (Chinese), 2008, 16(3):464–474
Puyal J, Sage C, Demêmes D, et al. Distribution of alpha-amino-3-hydroxy-5-methyl-4 isoazolepropionic acid and N-methyl-D-aspartate receptor subunits in the vestibular and spiral ganglia of the mouse during early development. Brain Res Dev Brain Res, 2002,139(1): 51–57
Nordang L, Cestreicher E, Arnold W, et al. Glutamate is the afferent neurotransmitter in the human cochlea. Acta Otolaryngol, 2000,120(3):59–62
Bieńkowski P, Scińska A, Kostowski W. Ototoxic mechanism of aminoglycoside antibiotics—role of glutaminergic NMDA receptors. Pol Merkur Lekarski, 2000,9(52):713–715
Santamaria A, Salvatierra-Sánchez R, Roman BV, et al. Protective effect of the antioxidant selenium on quinolinic acid-induced neurotoxicity in rat: in vitro and in vivo studies. J Neurochem, 2003,86(2):479–488
Santamaria D, Gonzalez VE, Rios C, et al. NcG-nitro-L-arginine, a nitric oxide synthase inhibitor, antagonizes quinolinic acid-induced neurotoxicity and oxidative stress in rat striatal slices. Neurochem Res, 1999,24(7):843–848
Xu ZW, Chen SJ, Lu ZH, et al. Neuroprotective effect of magnesium sulfate on neuron cell. Shi Yong Lin Chuang Er Ke Xue Za Zhi (Chinese), 2004,19(1):49–51
Yan KS, Xue QH, Zhang JH, et al. Protection of magnesium in the spiral ganglion neuron damage induced by glutamate. National Med J China (Chinese), 2006,86(22):1572–1574
Author information
Authors and Affiliations
Corresponding author
Additional information
The authors contributed equally to this work.
This project was supported by a grant from the National Natural Sciences Foundation of China (No. 30872866).
Rights and permissions
About this article
Cite this article
Xiao, H., Yang, C., He, Y. et al. Neurotoxicity of quinolinic acid to spiral ganglion cells in rats. J. Huazhong Univ. Sci. Technol. [Med. Sci.] 30, 397–402 (2010). https://doi.org/10.1007/s11596-010-0364-1
Received:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11596-010-0364-1