Alpha2-adrenergic receptors in spiral ganglion neurons may mediate protective effects of brimonidine and yohimbine against glutamate and hydrogen peroxide toxicity

Cai, Jinfang; Li, Jianfeng; Liu, W.; Han, Yuechen; Wang, H.

doi:10.1016/j.neuroscience.2012.10.004

Cited by 11 publications

(21 citation statements)

References 57 publications

(61 reference statements)

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“…Therefore, the molecular mechanisms involved in brimonidine-mediated protection in the retina may be similar to those involved in HCs. Moreover, brimonidine acts as a neuroprotective agent for the spiral ganglion [Cai et al, 2013a], supporting the idea that brimonidine has protective activity in the inner ear.…”

Section: Brimonidine Protects Ohcs From Gentamicininduced Toxicitysupporting

confidence: 60%

“…This is important because it suggests that the protective effect of brimonidine requires activation of the α 2 -AR and hence is mediated by the α 2 -AR itself. Cai et al [2013a] found similar results in that yohimbine blocked the protective effects of brimonidine against glutamate and hydrogen peroxide toxicity. In the visual system, the protective effects of brimonidine were also blocked by yohimbine [Lai et al, 2002].…”

Section: Brimonidine Protects Ohcs From Gentamicininduced Toxicitysupporting

confidence: 59%

“…Before exposure to gentamicin, the OCs were pretreated with brimonidine (1, 10, or 100 μ M ) and yohimbine (10 μ M ) for 20-24 h. Yohimbine is an α 2 -AR antagonist that has been used to block the effects of brimonidine that are mediated by the α 2 -AR [Cai et al, 2013a;Harun-Or-Rashid et al, 2014Lai et al, 2002]. The concentrations we used were based on a study that found that 10 μ M of yohimbine blocked the effects of several concentrations of brimonidine (0.01-1 μ M ) [Cai et al, 2013a].…”

Section: Oc Dissectionmentioning

confidence: 99%

“…For the Western blot analysis, 3 biological replicates were used for the 24-h incubation, and 2 biological replicates were used for the 8-h incubation. An incubation time of 24 h was chosen because Erk1/2 activation was observed in previous studies after 24 h [Cai et al, 2013a;Harun-Or-Rashid et al, 2015]. Chung et al [2006] observed Akt activation after exposure to gentamicin for 6 h. We decided to investigate Akt activation after exposure to gentamicin for 8 h.…”

Section: Immunoblottingmentioning

confidence: 99%

“…In addition to these molecular mechanisms, brimonidine has also been shown to have neuroprotective properties via N-methyl-D -aspartate (NMDA) inhibition [Dong et al, 2008;Han and Wu, 2002], growth factor upregulation [Gao et al, 2002;Kim et al, 2007;Lonngren et al, 2006], and involvement in apoptotic pathways [Cai et al, 2013a;Lai et al, 2002]. Furthermore, brimonidine inhibits protein kinase A [Grueb et al, 2008].…”

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confidence: 99%

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Brimonidine Protects Auditory Hair Cells from in vitro-Induced Toxicity of Gentamicin

2017

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Brimonidine, an alpha-2 adrenergic receptor (α₂-AR) agonist, has neuroprotective effects in the visual system and in spiral ganglion neurons. Auditory hair cells (HCs) express all 3 α₂-AR subtypes, but their roles in HCs remain unknown. This study investigated the effects of brimonidine on auditory HCs that were also exposed to gentamicin, which is toxic to HCs. Organ of Corti explants were exposed to gentamicin in the presence or absence of brimonidine, and the α₂-AR protein expression levels and Erk1/2 and Akt phosphorylation levels were determined. Brimonidine had a protective effect on auditory HCs against gentamicin-induced toxicity that was blocked by yohimbine. This suggested that the protective effect of brimonidine on HCs was mediated by the α₂-AR. None of the treatments altered α₂-AR protein expression levels, and brimonidine did not significantly change the activation levels of the Erk1/2 and Akt proteins. These observations indicated that brimonidine, acting directly via α₂-AR, protects HCs from gentamicin-induced toxicity. Therefore, brimonidine shows potential for preventing or treating sensorineural hearing loss.

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Section: Brimonidine Protects Ohcs From Gentamicininduced Toxicitysupporting

confidence: 60%

Section: Brimonidine Protects Ohcs From Gentamicininduced Toxicitysupporting

confidence: 59%

Section: Oc Dissectionmentioning

confidence: 99%

Section: Immunoblottingmentioning

confidence: 99%

mentioning

confidence: 99%

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Brimonidine Protects Auditory Hair Cells from in vitro-Induced Toxicity of Gentamicin

2017

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Utricular dysfunction in patients with orthostatic hypotension

Kim

Lee

et al. 2022

Clin Auton Res

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Immunohistochemical Localization of α2-Adrenergic Receptors in the Neonatal Rat Cochlea and the Vestibular Labyrinth

Cai

Mao

et al. 2013

J Mol Neurosci

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The α2-adrenergic receptors (α2-ARs), which mediate physiological responses to noradrenaline and adrenaline, are encoded by three different genes but all are coupled to the Gi/Go subfamily of G proteins. The present study investigated the localization of three subtypes, i.e., α2a-, α2b-, and α2c-ARs, in cochlea and vestibular labyrinth in rat in the early postnatal period by immunohistochemistry. The results showed that α2-ARs were widely distributed in regions, including the organ of Corti, spiral ganglion neurons, stria vascularis, crista ampullaris, Scarpa's ganglion, utricle, and Reissner's membrane. Furthermore, the cellular locations of α2-ARs between different cell subtypes as well as receptor subtypes and different observed time points also had diversity. α2a-AR mainly targeted to nuclei at postnatal ages (P)3. While at P(8), only ganglion neurons maintained this character whereas other cell types expressed α2a-AR mainly in plasma membrane. The α2b- and α2c-ARs exhibited predominantly in plasma membrane. Compared with P(8), α2c-AR was not present at stria vascularis at P(3). Overall, our observations indicated that there was region-specific regulation of α2-ARs development in cochlea and vestibular labyrinth. In addition, the extensive expressions of α2-ARs established a significant foundation for the exploration of the function of α2-ARs in cochlea and vestibular labyrinth.

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Alpha2-adrenergic receptors in spiral ganglion neurons may mediate protective effects of brimonidine and yohimbine against glutamate and hydrogen peroxide toxicity

Cited by 11 publications

References 57 publications

Brimonidine Protects Auditory Hair Cells from in vitro-Induced Toxicity of Gentamicin

Brimonidine Protects Auditory Hair Cells from in vitro-Induced Toxicity of Gentamicin

Utricular dysfunction in patients with orthostatic hypotension

Immunohistochemical Localization of α2-Adrenergic Receptors in the Neonatal Rat Cochlea and the Vestibular Labyrinth

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