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Inhibition of the A...
Inhibition of the Activation and Recruitment of Microglia-Like Cells Protects Against Neomycin-Induced Ototoxicity
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Sun, S. (författare)
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Yu, H. Q. (författare)
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Yu, H. (författare)
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Mei, H. L. (författare)
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Ni, W. L. (författare)
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Zhang, Y. P. (författare)
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Guo, L. (författare)
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He, Y. Z. (författare)
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Xue, Z. (författare)
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Ni, Y. S. (författare)
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Li, J. (författare)
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Feng, Y. (författare)
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Chen, Y. (författare)
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- Shao, Linus Ruijin, 1964 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology
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Chai, R. J. (författare)
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Li, H. W. (författare)
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(creator_code:org_t)
- 2014-05-01
- 2015
- Engelska.
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Ingår i: Molecular Neurobiology. - : Springer Science and Business Media LLC. - 0893-7648 .- 1559-1182. ; 51:1, s. 252-267
- Relaterad länk:
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- One of the most unfortunate side effects of aminoglycoside (AG) antibiotics such as neomycin is that they target sensory hair cells (HCs) and can cause permanent hearing impairment. We have observed HC loss and microglia-like cell (MLC) activation in the inner ear (cochlea) following neomycin administration. We focused on CX3CL1, a membrane-bound glycoprotein expressed on neurons and endothelial cells, as a way to understand how the MLCs are activated and the role these cells play in HC loss. CX3CL1 is the exclusive ligand for CX3CR1, which is a chemokine receptor expressed on the surface of macrophages and MLCs. In vitro experiments showed that the expression levels of CX3CL1 and CX3CR1 increased in the cochlea upon neomycin treatment, and CX3CL1 was expressed on HCs, while CX3CR1 was expressed on MLCs. When cultured with 1 mu g/mL exogenous CX3CL1, MLCs were activated by CX3CL1, and the cytokine level was increased in the cochleae leading to apoptosis in the HCs. In CX3CR1 knockout mice, a significantly greater number of cochlear HCs survived than in wild-type mice when the cochlear explants were cultured with neomycin in vitro. Furthermore, inhibiting the activation of MLCs with minocycline reduced the neomycin-induced HC loss and improved the hearing function in neomycin-treated mice in vivo. Our results demonstrate that CX3CL1-induced MLC activation plays an important role in the induction of HC death and provide evidence for CX3CL1 and CX3CR1 as promising new therapeutic targets for the prevention of hearing loss.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Nyckelord
- Microglia-like cell
- Hearing loss
- Hair cell death
- CX3CL1
- SENSORINEURAL HEARING-LOSS
- NEUROPATHIC PAIN
- SPINAL-CORD
- PROINFLAMMATORY CYTOKINES
- INFLAMMATORY RESPONSE
- FRACTALKINE RECEPTOR
- HIPPOCAMPAL-NEURONS
- CX3C CHEMOKINE
- HAIR-CELLS
- RAT ORGAN
- Neurosciences
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Sun, S.
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Yu, H. Q.
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Yu, H.
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Mei, H. L.
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Ni, W. L.
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Zhang, Y. P.
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visa fler...
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Guo, L.
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He, Y. Z.
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Xue, Z.
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Ni, Y. S.
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Li, J.
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Feng, Y.
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Chen, Y.
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Shao, Linus Ruij ...
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Chai, R. J.
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Li, H. W.
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visa färre...
- Om ämnet
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Medicinska och f ...
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och Neurovetenskaper
- Artiklar i publikationen
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Molecular Neurob ...
- Av lärosätet
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Göteborgs universitet