Effect and Mechanism of BDNF/TrkB Signaling on Vestibular Compensation

Brain-derived neurotrophic factor (BDNF) regulates neuronal plasticity by targeting the tyrosine kinase B receptor (TrkB) receptor, but limited researches concentrate on the role of BDNF/TrkB signaling in vestibular compensation. In this study, rats with unilateral vestibular dysfunction were establ...

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Autores principales: Dehong Mao, Zhongmei He, Wei Xuan, Jiao Deng, Weichun Li, Xiaoying Fang, Linglong Li, Feng Zhang
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Publicado: Taylor & Francis Group 2021
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spelling oai:doaj.org-article:3384920ce9fa41a491d2e5c82014e42d2021-11-04T15:51:54ZEffect and Mechanism of BDNF/TrkB Signaling on Vestibular Compensation2165-59792165-598710.1080/21655979.2021.1997565https://doaj.org/article/3384920ce9fa41a491d2e5c82014e42d2021-10-01T00:00:00Zhttp://dx.doi.org/10.1080/21655979.2021.1997565https://doaj.org/toc/2165-5979https://doaj.org/toc/2165-5987Brain-derived neurotrophic factor (BDNF) regulates neuronal plasticity by targeting the tyrosine kinase B receptor (TrkB) receptor, but limited researches concentrate on the role of BDNF/TrkB signaling in vestibular compensation. In this study, rats with unilateral vestibular dysfunction were established by unilateral labyrinthectomy (UL) and infusion with siBDNF or 7, 8-Dihydroxyflavone (7,8-DHF, a TrkB receptor agonist). The behavioral scores of rats with vestibular deficits were determined and the rotarod test was performed after UL. BDNF and TrkB levels after UL were determined by western blot and quantitative reverse transcription PCR (qRT-PCR). 5-bromo-2ʹ-deoxyuridine (BrdU)-positive cells (newly generated cells) and GAD67-positive cells (GABAergic neurons) were identified by immunohistochemistry. Glial fibrillary acidic protein (GFAP) (astrocyte marker)-positive cells were identified and GABA type A receptor (GABAAR) expression was detected by immunofluorescence. We found that after UL, BDNF and TrkB levels were up-regulated with a maximum value at 4 h, and then progressively down-regulated during 4 h~7 d. Blocking BDNF/TrkB signaling inhibited the recovery from vestibular deficits, decreased the numbers of newly generated cells and astrocytes in medial vestibular nucleus (MVN), inferior vestibular nerve (IVN), superior vestibular nerve (SVN) and lateral vestibular nucleus (LVN), and disrupted the balances of GABAergic neurons and GABAAR expressions in the left (lesioned) side and right (intact) side of MVN, whereas activation of BDNF/TrkB signaling caused opposite results. The current study indicated that BDNF/TrkB signaling avails vestibular compensation, depending on the number of newly generated cells and astrocytes, the rebalance of GABAergic neurons, and GABAAR expression in bilateral MVN.Dehong MaoZhongmei HeWei XuanJiao DengWeichun LiXiaoying FangLinglong LiFeng ZhangTaylor & Francis Grouparticlebdnf/trkb signalingvestibular compensationastrocytegabaergic neurongabaarBiotechnologyTP248.13-248.65ENBioengineered, Vol 0, Iss 0 (2021)
institution DOAJ
collection DOAJ
language EN
topic bdnf/trkb signaling
vestibular compensation
astrocyte
gabaergic neuron
gabaar
Biotechnology
TP248.13-248.65
spellingShingle bdnf/trkb signaling
vestibular compensation
astrocyte
gabaergic neuron
gabaar
Biotechnology
TP248.13-248.65
Dehong Mao
Zhongmei He
Wei Xuan
Jiao Deng
Weichun Li
Xiaoying Fang
Linglong Li
Feng Zhang
Effect and Mechanism of BDNF/TrkB Signaling on Vestibular Compensation
description Brain-derived neurotrophic factor (BDNF) regulates neuronal plasticity by targeting the tyrosine kinase B receptor (TrkB) receptor, but limited researches concentrate on the role of BDNF/TrkB signaling in vestibular compensation. In this study, rats with unilateral vestibular dysfunction were established by unilateral labyrinthectomy (UL) and infusion with siBDNF or 7, 8-Dihydroxyflavone (7,8-DHF, a TrkB receptor agonist). The behavioral scores of rats with vestibular deficits were determined and the rotarod test was performed after UL. BDNF and TrkB levels after UL were determined by western blot and quantitative reverse transcription PCR (qRT-PCR). 5-bromo-2ʹ-deoxyuridine (BrdU)-positive cells (newly generated cells) and GAD67-positive cells (GABAergic neurons) were identified by immunohistochemistry. Glial fibrillary acidic protein (GFAP) (astrocyte marker)-positive cells were identified and GABA type A receptor (GABAAR) expression was detected by immunofluorescence. We found that after UL, BDNF and TrkB levels were up-regulated with a maximum value at 4 h, and then progressively down-regulated during 4 h~7 d. Blocking BDNF/TrkB signaling inhibited the recovery from vestibular deficits, decreased the numbers of newly generated cells and astrocytes in medial vestibular nucleus (MVN), inferior vestibular nerve (IVN), superior vestibular nerve (SVN) and lateral vestibular nucleus (LVN), and disrupted the balances of GABAergic neurons and GABAAR expressions in the left (lesioned) side and right (intact) side of MVN, whereas activation of BDNF/TrkB signaling caused opposite results. The current study indicated that BDNF/TrkB signaling avails vestibular compensation, depending on the number of newly generated cells and astrocytes, the rebalance of GABAergic neurons, and GABAAR expression in bilateral MVN.
format article
author Dehong Mao
Zhongmei He
Wei Xuan
Jiao Deng
Weichun Li
Xiaoying Fang
Linglong Li
Feng Zhang
author_facet Dehong Mao
Zhongmei He
Wei Xuan
Jiao Deng
Weichun Li
Xiaoying Fang
Linglong Li
Feng Zhang
author_sort Dehong Mao
title Effect and Mechanism of BDNF/TrkB Signaling on Vestibular Compensation
title_short Effect and Mechanism of BDNF/TrkB Signaling on Vestibular Compensation
title_full Effect and Mechanism of BDNF/TrkB Signaling on Vestibular Compensation
title_fullStr Effect and Mechanism of BDNF/TrkB Signaling on Vestibular Compensation
title_full_unstemmed Effect and Mechanism of BDNF/TrkB Signaling on Vestibular Compensation
title_sort effect and mechanism of bdnf/trkb signaling on vestibular compensation
publisher Taylor & Francis Group
publishDate 2021
url https://doaj.org/article/3384920ce9fa41a491d2e5c82014e42d
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