Dexamethasone protects against arsanilic acid‑induced rat vestibular dysfunction through the BDNF and JNK 1/2 signaling pathways

Luo,Yan; Zhang,Daogong; Chen,Yueling; Cao,Zhongsheng; Fan,Zhaomin

doi:10.3892/mmr.2019.9835

Dexamethasone protects against arsanilic acid‑induced rat vestibular dysfunction through the BDNF and JNK 1/2 signaling pathways

Authors:
- Yan Luo
- Daogong Zhang
- Yueling Chen
- Zhongsheng Cao
- Zhaomin Fan
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Affiliations: Department of Otolaryngology‑Head and Neck Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China, Department of Otolaryngology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, P.R. China
Published online on: January 8, 2019 https://doi.org/10.3892/mmr.2019.9835
Pages: 1781-1790

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Abstract

The brain‑derived neurotrophic factor (BDNF) and c‑Jun NH 2‑terminal kinase (JNK) signaling pathways are therapeutic targets to prevent degeneration in the central nervous system. Dexamethasone (DXMS), a glucocorticoid, protects against vestibular brain injury, however, the molecular mechanisms have yet to be fully elucidated. To investigate whether the BDNF and JNK signaling pathways are involved in the protective effects of DXMS in rats with vestibular dysfunction, a rat model of severe vestibular deficits was established by middle ear injection of arsanilic acid (AA; 100 mg/ml; 0.05 ml). After 3 days, rat symptoms and behavior scores with vestibular disorders were detected. In brain tissues, histopathological alterations, cell apoptosis, expression levels and patterns of BDNF signaling pathway‑associated BDNF, tyrosine receptor kinase B (TrKB) and K+/Cl‑ cotransporter isoform 2 (KCC2), and the expression of apoptosis‑related cleaved‑caspase 3 and the JNK signaling pathway were detected. It was identified that DXMS relieved AA‑induced vestibular dysfunction, leading to improvement in rat behavior scores to normal levels, minimizing brain damage at the histopatholojnnkngical level, reducing cell apoptosis, enhancing the expression of BDNF, TrKB and KCC2, and downregulating cleaved‑caspase 3 and phosphorylated‑JNK1/2 in brain tissues. Together, these findings indicated the protective effect of DXMS on AA‑induced rat vestibular dysfunction, and that activating BDNF and inhibiting JNK singling pathways were the underlying mechanisms. In addition, with additional treatment of mifepristone (RU486), a specific glucocorticoid agonist, all the events elicited by DXMS mentioned above in the AA‑treated rat rats were reversed. In conclusion, DXMS was identified as a therapeutic agent targeting the BDNF and JNK singling pathways for AA‑induced rat vestibular dysfunction.

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