PMID- 30628712
OWN - NLM
STAT- MEDLINE
DCOM- 20190531
LR  - 20190531
IS  - 1791-3004 (Electronic)
IS  - 1791-2997 (Linking)
VI  - 19
IP  - 3
DP  - 2019 Mar
TI  - Dexamethasone protects against arsanilic acid‑induced rat vestibular dysfunction 
      through the BDNF and JNK 1/2 signaling pathways.
PG  - 1781-1790
LID - 10.3892/mmr.2019.9835 [doi]
AB  - 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.
FAU - Luo, Yan
AU  - Luo Y
AD  - Department of Otolaryngology‑Head and Neck Surgery, Shandong Provincial Hospital 
      Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.
FAU - Zhang, Daogong
AU  - Zhang D
AD  - Department of Otolaryngology‑Head and Neck Surgery, Shandong Provincial Hospital 
      Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.
FAU - Chen, Yueling
AU  - Chen Y
AD  - Department of Otolaryngology‑Head and Neck Surgery, Shandong Provincial Hospital 
      Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.
FAU - Cao, Zhongsheng
AU  - Cao Z
AD  - Department of Otolaryngology, The Second Affiliated Hospital of Soochow 
      University, Suzhou, Jiangsu 215004, P.R. China.
FAU - Fan, Zhaomin
AU  - Fan Z
AD  - Department of Otolaryngology‑Head and Neck Surgery, Shandong Provincial Hospital 
      Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20190108
PL  - Greece
TA  - Mol Med Rep
JT  - Molecular medicine reports
JID - 101475259
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (RNA, Messenger)
RN  - 7S5I7G3JQL (Dexamethasone)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - EC 3.4.22.- (Caspase 3)
RN  - UDX9AKS7GM (Arsanilic Acid)
SB  - IM
MH  - Animals
MH  - Arsanilic Acid
MH  - Brain/pathology
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Caspase 3/genetics/metabolism
MH  - Dexamethasone/pharmacology/*therapeutic use
MH  - *MAP Kinase Signaling System/drug effects
MH  - Male
MH  - RNA, Messenger/genetics/metabolism
MH  - Rats, Sprague-Dawley
MH  - Receptor, trkB/metabolism
MH  - Vestibular Diseases/*chemically induced/*drug therapy/metabolism/physiopathology
EDAT- 2019/01/11 06:00
MHDA- 2019/06/01 06:00
CRDT- 2019/01/11 06:00
PHST- 2018/04/08 00:00 [received]
PHST- 2018/11/12 00:00 [accepted]
PHST- 2019/01/11 06:00 [pubmed]
PHST- 2019/06/01 06:00 [medline]
PHST- 2019/01/11 06:00 [entrez]
AID - 10.3892/mmr.2019.9835 [doi]
PST - ppublish
SO  - Mol Med Rep. 2019 Mar;19(3):1781-1790. doi: 10.3892/mmr.2019.9835. Epub 2019 Jan 
      8.