Effect of Ginkgo Biloba Extract on N-Methyl-D-Aspartic Acid Receptor Subunit 2B Expression in a Salicylate-Induced Ototoxicity Model
2
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Objectives. Sodium salicylate (SS) is well known for its ototoxic properties that induce functional and morphological changes in the cochlea and brain. Ginkgo biloba extract (GBE) has been widely used for treatment of various neurodegenerative diseases; however, its effects on salicylate-induced ototoxicity remain unclear. Herein, we examined the effects of EGb 761 (EGb), a standard form of GBE, on the plasticity of the N-methyl-D-aspartate receptor subunit 2B (GluN2B) in the inferior colliculus (IC) following SS administration. Methods. Seven-week-old Sprague Dawley rats (n=24) were randomly allocated to control, SS, EGb, and EGb+SS groups. The SS group received a single intraperitoneal SS injection (350 mg/kg), the EGb group received EGb orally for 5 consecutive days (40 mg/kg), and the EGb+SS group received EGb for 5 consecutive days, followed by an SS injection. The auditory brainstem responses (ABRs) were assessed at baseline and 2 hours after SS administration. GluN2B expression was examined by Western blot and immunohistochemistry. Results. There were no significant differences in ABR threshold shifts among the groups. The expression of the GluN2B protein normalized by which of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) was significantly lower in the EGb+SS group, as compared to the SS group (P=0.012). Weak and diffused GluN2B immunoreactivity was detected in the IC neural cells of the EGb+SS group, while those of the SS group exhibited strong and diffused GluN2B positivity. Conclusion. EGb may play a role in regulating the GluN2B expression in the IC of salicylate-induced ototoxicity model.
Abstract
Objectives. Sodium salicylate (SS) is well known for its ototoxic properties that induce functional and morphological changes in the cochlea and brain. Ginkgo biloba extract (GBE) has been widely used for treatment of various neurodegenerative diseases; however, its effects on salicylate-induced ototoxicity remain unclear. Herein, we examined the effects of EGb 761 (EGb), a standard form of GBE, on the plasticity of the N-methyl-D-aspartate receptor subunit 2B (GluN2B) in the inferior colliculus (IC) following SS administration. Methods. Seven-week-old Sprague Dawley rats (n=24) were randomly allocated to control, SS, EGb, and EGb+SS groups. The SS group received a single intraperitoneal SS injection (350 mg/kg), the EGb group received EGb orally for 5 consecutive days (40 mg/kg), and the EGb+SS group received EGb for 5 consecutive days, followed by an SS injection. The auditory brainstem responses (ABRs) were assessed at baseline and 2 hours after SS administration. GluN2B expression was examined by Western blot and immunohistochemistry. Results. There were no significant differences in ABR threshold shifts among the groups. The expression of the GluN2B protein normalized by which of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) was significantly lower in the EGb+SS group, as compared to the SS group (P=0.012). Weak and diffused GluN2B immunoreactivity was detected in the IC neural cells of the EGb+SS group, while those of the SS group exhibited strong and diffused GluN2B positivity. Conclusion. EGb may play a role in regulating the GluN2B expression in the IC of salicylate-induced ototoxicity model.
참고문헌 (24)
- Sinha GP, "Organization of membrane motor in outer hair cells : an atomic force microscopic study", Pflugers Arch, 459(3), pp.427~439 (2010)
- Guitton MJ, "Salicylate induces tinnitus through activation of cochlear NMDA receptors", J Neurosci, 23(9), pp.3944~3952 (2003)
- Parsons MP, "Extrasynaptic NMDA receptor involvement in central nervous system disorders", Neuron, 82(2), pp.279~293 (2014)
- Oestreicher E, "Rational pharmacotherapy of the inner ear", pp.131~139 (2002), Karger Publishers
- Imsuwansri T, "Glutamate receptor antagonists for tinnitus", Cochrane Database Syst Rev, 10, pp.CD012391~ (2016)
- Mitchell JA, "Selectivity of nonsteroidal antiinflammatory drugs as inhibitors of constitutive and inducible cyclooxygenase", Proc Natl Acad Sci U S A, 90(24), pp.11693~11697 (1993)
- Hu SS, "Expression of immediateearly genes in the inferior colliculus and auditory cortex in salicylateinduced tinnitus in rat", Eur J Histochem, 58(1), pp.2294~ (2014)
- Szasz BK, "Converging effects of Ginkgo biloba extract at the level of transmitter release, NMDA and sodium currents and dendritic spikes", Planta Med, 74(10), pp.1235~1239 (2008)
- Dave JR, "Studies on neuronal apoptosis in primary forebrain cultures : neuroprotective", anti-apoptotic action of NR2B NMDA antagonists, 2003, pp.5(4), 255~264
- Ahlemeyer B, "Pharmacological studies supporting the therapeutic use of Ginkgo biloba extract for Alzheimer’s disease", Pharmacopsychiatry, 1, pp.S8~14 (2003)
- Li S, "Effects of Ginkgo biloba extracts on NMDA-activated currents in acutely isolated hippocampal neurons of the rat", Phytother Res, 25(1), pp.137~141 (2011)
- National Research Council of the National Academies, "Guide for the care and use of laboratory animals" (2010), National Academies Press
- Sheppard A, "Review of salicylate-induced hearing loss, neurotoxicity, tinnitus and neuropathophysiology", Acta Otorhinolaryngol Ital, 34(2), pp.79~93 (2014)
- 임기정, "Expression of Insulin-like Growth Factors in a Mouse Model of Salicylate Ototoxicity", Clinical and Experimental Otorhinolaryngology, 3(3), pp.115~121 (2010), 대한이비인후과학회
- Choi IS, "Effects of salicylate on ABR and ECoG in guinea pig", Korean J Otolaryngol Head Neck Surg, 42(3), pp.290~297 (1999)
- Fioretti A, "New trends in tinnitus management", Open Neurol J, 5, pp.12~17 (2011)
- Hwang JH, "Expression of COX-2 and NMDA receptor genes at the cochlea and midbrain in salicylate-induced tinnitus", Laryngoscope, 121(2), pp.361~364 (2011)
- Hu SS, "Expression of immediateearly genes in the dorsal cochlear nucleus in salicylate-induced tinnitus", Eur Arch Otorhinolaryngol, 273(2), pp.325~332 (2016)
- Yashiro K, "Regulation of NMDA receptor subunit expression and its implications for LTD, LTP, and metaplasticity", Neuropharmacology, 55(7), pp.1081~1094 (2008)
- Zhao J, "Up-regulation of Ca(2+)", CaMKII, Mol Cell Biochem, pp.2018, 448(1-2)[DOI]
- Huang DS, "Treatment with a Ginkgo biloba extract, EGb 761, inhibits excitotoxicity in an animal model of spinocerebellar ataxia type 17", Drug Des Devel Ther, 10, pp.723~731 (2016)
- Wheeler D, "Tumor necrosis factor-alpha-induced neutral sphingomyelinase-2modulates synaptic plasticity by controlling the membrane insertion of NMDA receptors", J Neurochem, 109(5), pp.1237~1249 (2009)
- Hwang JH, "Effects of C-phycocyanin and Spirulina on salicylate-induced tinnitus, expression of NMDA receptor and inflammatory genes", PLoS One, 8(3), pp.e58215~ (2013)
- Kaur S, "Anti-inflammatory effects of Ginkgo biloba extract against trimethyltin-induced hippocampal neuronal injury", Inflammopharmacology, 26(1), pp.87~104 (2018)