Pain Mechanisms and Sensory NeuroscienceResearch PaperSalicylate-induced degeneration of cochlea spiral ganglion neurons-apoptosis signaling
Section snippets
Cochlear cultures
Cochlear organotypic cultures were prepared from postnatal day 3 SASCO Sprague–Dawley rats as previously described (Ding et al., 2002, McFadden et al., 2003). Following decapitation, the cochlea was carefully removed and the organ of Corti and SGN were isolated and transferred onto rat tail collagen gel (type I rat-tail collagen (Collaborative Research, 3.76 mg/ml in 0.02 N acetic acid), 10×BME (basal medium Eagle) with 2% sodium carbonate in a 9:1:1 ratio). A 15-μL drop of the collagen gel was
SS damages nerve fibers
Fig. 1A–D illustrates the typical status of the hair cells and nerve fibers in control medium and cultures treated with 1, 3, or 5 mM of SS for 48 h or 10 mM SS for 96 h. Three rows of OHC and one row of IHC were present in the controls; many nerve fiber fascicles project radially and end near the IHC; a few fibers also project to the OHC (Fig. 1A). Treatment with 1 mM SS had no noticeable effect on OHC or IHC; however, the density of nerve fiber fascicles projecting towards the hair cells was
Discussion
The 1 and 3 mM doses of SS used this study are comparable to those observed in cochlear perilymph and cerebrospinal fluid of animals with hearing loss and tinnitus induced by systemic administration of a high dose of salicylate (Jastreboff et al., 1986, Jastreboff et al., 1988, Boettcher and Salvi, 1991, Lobarinas et al., 2006, Yang et al., 2007, Sun et al., 2009). Our results indicate that SS causes a dose-dependent shrinkage of SGN soma, a morphological feature of cells undergoing apoptosis,
Conclusion
Aspirin, whose active component is salicylate, is one of the most widely used over-the-counter medications; however, its is not recommended for use in children since it has been implicated in Reye's syndrome, a childhood disorder characterized by encephalopathy and hyperammonemia (Trost and Lemasters, 1997, Lemberg et al., 2009). Millions of patients (e.g. rheumatoid arthritis) chronically self-administer high doses of the aspirin for pain relief, inflammation and other health problems. High
Acknowledgments
Supported in part by grants from NIH (R01DC009091; R01DC009219) and Tinnitus Research Initiative.
References (104)
- et al.
Apo2L/TRAIL: apoptosis signaling, biology, and potential for cancer therapy
Cytokine Growth Factor Rev
(2003) - et al.
Effects of salicylate on spontaneous activity in inferior colliculus brain slices
Neurosci Res
(2004) - et al.
Effects of salicylate application on the spontaneous activity in brain slices of the mouse cochlear nucleus, medial geniculate body and primary auditory cortex
Hear Res
(2008) - et al.
Salicylate ototoxicity: review and synthesis
Am J Otolaryngol
(1991) - et al.
A necessary role for cell shrinkage in apoptosis
Biochem Pharmacol
(1998) Auditory sensori-neural alterations induced by salicylate
Prog Neurobiol
(2000)- et al.
Salicylate-induced abnormal activity in the inferior colliculus of rats
Hear Res
(1995) - et al.
Mitochondria localization and dimerization are required for CIDE-B to induce apoptosis
J Biol Chem
(2000) - et al.
The distinct roles of TRAF2 and RIP in IKK activation by TNF-R1: TRAF2 recruits IKK to TNF-R1 while RIP mediates IKK activation
Immunity
(2000) - et al.
Cell death after co-administration of cisplatin and ethacrynic acid
Hear Res
(2007)