Molecular regulation of auditory hair cell death and approaches to protect sensory receptor cells and/or stimulate repair following acoustic trauma

Dinh, Christine T.; Goncalves, Stefania; Bas, Esperanza; Water, Thomas R. Van De; Zine, Azel

doi:10.3389/fncel.2015.00096

Cited by 77 publications

(92 citation statements)

References 202 publications

(267 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…JNK and p38, members of the mitogen‐activated protein kinase (MAPK) family, have been proven critical in the cell survival and cellular apoptosis pathways. Oxidative stress, UV radiation and inflammatory cytokines such as IL‐1β and TNF‐α activate the JNK/p38 cascades . Activation of the JNK/p38 signalling pathway activates Bax to induce apoptosis .…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

PI3K/AKT/JNK/p38 signalling pathway‐mediated neural apoptosis in the prefrontal cortex of mice is involved in the antidepressant‐like effect of pioglitazone

Chen

et al. 2018

Clin Exp Pharma Physio

View full text Add to dashboard Cite

Summary Numerous studies have reported that inflammation is involved in the pathophysiology of depression. Pioglitazone, a PPAR‐γ agonist, has potential anti‐inflammatory and antidepressive effects. However, the underlying molecular mechanisms of the antidepressant‐like effect of pioglitazone on an inflammation‐related mouse model of depression remain to be fully elucidated. Herein, we aimed to explore the effects of pioglitazone on depressive‐like behaviours of mice exposed to lipopolysaccharides (LPS), and elucidate the underlying mechanisms. We assessed behaviour changes of mice pretreated with pioglitazone exposed to LPS. Additionally, neural apoptosis, and the expression of apoptosis‐related (cleaved caspase‐3, Bax, Bcl‐2, cyt c) and signalling proteins (AKT, JNK, p38) were assessed in the prefrontal cortex (PFC) of these mice. Furthermore, we assessed the influence of anisomycin, a JNK/p38 agonist, and LY294002, a PI3K/AKT inhibitor, on the antidepressant‐like effect of pioglitazone in mice. We show that pioglitazone pretreatment (20 mg/kg, intragastrically) attenuated LPS‐induced (10 ng/μL per site) depressive‐like behaviours. GW9662, a PPAR‐γ antagonist, significantly blocked the antidepressant‐like effect of pioglitazone. Furthermore, at the molecular level, pioglitazone significantly reversed, via PPAR‐γ‐dependent increase in neural apoptosis in the PFC of mice, accompanied by upregulation of the PI3K/AKT pathway and down‐regulation of the JNK/p38 pathway. Moreover, both anisomycin and LY294002 abrogated the antidepressant‐like effect of pioglitazone.; In conclusion, our results showed that PI3K/AKT/JNK/p38 signalling pathway‐mediated neural apoptosis in the PFC of mice may be involved in the antidepressant‐like effect of pioglitazone. This provides novel insights into and therapeutic targets for inflammation‐related depression.

show abstract

Section: Discussionmentioning

confidence: 99%

“…Then, GW9662 significantly cascades. 31 Activation of the JNK/p38 signalling pathway activates Bax to induce apoptosis. 32,33 In an in vitro experiment, activated JNK/p38 cascades and apoptosis were observed simultaneously in both neuronal-like cells and PC12 cells exposed to LPS.…”

Section: Discussionmentioning

confidence: 99%

PI3K/AKT/JNK/p38 signalling pathway‐mediated neural apoptosis in the prefrontal cortex of mice is involved in the antidepressant‐like effect of pioglitazone

Chen

et al. 2018

Clin Exp Pharma Physio

View full text Add to dashboard Cite

show abstract

“…Hair cells exposed to acoustic trauma have been shown to undergo apoptotic cell death, necrotic cell death, or a combination of the two46. To determine whether hair-cell death in iGluR-agonist exposed hair cells appears characteristically apoptotic or necrotic, I examined changes in hair-cell morphology in ngn1 morphant larvae to either KA or NMDA.…”

Section: Resultsmentioning

confidence: 99%

Excessive activation of ionotropic glutamate receptors induces apoptotic hair-cell death independent of afferent and efferent innervation

Sheets

2017

Sci Rep

View full text Add to dashboard Cite

Accumulation of excess glutamate plays a central role in eliciting the pathological events that follow intensely loud noise exposures and ischemia-reperfusion injury. Glutamate excitotoxicity has been characterized in cochlear nerve terminals, but much less is known about whether excess glutamate signaling also contributes to pathological changes in sensory hair cells. I therefore examined whether glutamate excitotoxicity damages hair cells in zebrafish larvae exposed to drugs that mimic excitotoxic trauma. Exposure to ionotropic glutamate receptor (iGluR) agonists, kainic acid (KA) or N-methyl-D-aspartate (NMDA), contributed to significant, progressive hair cell loss in zebrafish lateral-line organs. To examine whether hair-cell loss was a secondary effect of excitotoxic damage to innervating neurons, I exposed neurog1a morphants—fish whose hair-cell organs are devoid of afferent and efferent innervation—to KA or NMDA. Significant, dose-dependent hair-cell loss occurred in neurog1a morphants exposed to either agonist, and the loss was comparable to wild-type siblings. A survey of iGluR gene expression revealed AMPA-, Kainate-, and NMDA-type subunits are expressed in zebrafish hair cells. Finally, hair cells exposed to KA or NMDA appear to undergo apoptotic cell death. Cumulatively, these data reveal that excess glutamate signaling through iGluRs induces hair-cell death independent of damage to postsynaptic terminals.

show abstract

“…High-frequency sounds created by noise, such as rifle fire, that cause shock are typical of noise patterns that can induce AT; permanent hearing loss can occur following a single exposure without a temporary threshold shift [1,14,15] . SMA supports the inner ear's circulation.…”

Section: Discussionmentioning

confidence: 99%

“…It is widely accepted that biochemical changes or changes in the functional unity of the outer hair cells and auditory nerve fibers can precipitate cell destruction and hearing loss [1][2][3] . After noise exposure, outer hair cells are impaired [4] , and reactive oxygen levels increase in the cochlea [5] .…”

Section: Introductionmentioning

confidence: 99%

The Potential Protective Effects of 2-aminoethyl Diphenylborinate against Inner Ear Acoustic Trauma: Experimental Study Using Transmission and Scanning Electron Microscopy

Kaymakçı¹,

Acar²,

Burukoğlu³

et al. 2015

Int Adv Otol

View full text Add to dashboard Cite

OBJECTIVE:In this prospective experimental study, we investigated the preventive effects of 2-aminoethyl diphenylborinate (2-APB) in rats exposed to acoustic trauma (AT). Light microscopic, transmission electron microscopic (TEM), and scanning electron microscopic (SEM) examinations were performed. MATERIALS and METHODS:Eighteen healthy Wistar albino rats were divided into the following three groups: groups 1 (control), 2 (AT), and 3 (AT+APB). The rats in groups 2 and 3 were exposed to AT; in group 3 rats, 2-APB at 2 mg/kg was also administered, initially transperitoneally, after 10 min. RESULTS:During the light microscopic, TEM, and SEM examinations, the structures of the cochlear hair cells, stereocilia, and Deiter's cells were normal in the control group. In the AT group, the organ of Corti and proximate structures were damaged according to the light microscopic examination. During the TEM examination, intense cellular damage and stereocilia loss were detected, while during the SEM examination, extensive damage and stereocilia loss were observed. Decreased damage with preserved cochlear structure was detected during the light microscopic examination in the AT+APB group than in the AT group. During the TEM and SEM examinations, although stereocilia loss occurred in the AT+APB group, near-normal cell, cilia, and tectorial membrane structures were also observed in the AT+APB group compared with the AT group.CONCLUSION: 2-APB may have protective effects against AT damage of the cochlea. The main mechanism underlying this effect is the inhibition of the vasoconstriction of the cochlear spiral modiolar artery, thereby improving cochlear blood flow. We conclude that 2-APB may also be effective if used immediately following AT.

show abstract

Molecular regulation of auditory hair cell death and approaches to protect sensory receptor cells and/or stimulate repair following acoustic trauma

Cited by 77 publications

References 202 publications

PI3K/AKT/JNK/p38 signalling pathway‐mediated neural apoptosis in the prefrontal cortex of mice is involved in the antidepressant‐like effect of pioglitazone

PI3K/AKT/JNK/p38 signalling pathway‐mediated neural apoptosis in the prefrontal cortex of mice is involved in the antidepressant‐like effect of pioglitazone

Excessive activation of ionotropic glutamate receptors induces apoptotic hair-cell death independent of afferent and efferent innervation

The Potential Protective Effects of 2-aminoethyl Diphenylborinate against Inner Ear Acoustic Trauma: Experimental Study Using Transmission and Scanning Electron Microscopy

Contact Info

Product

Resources

About