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Neurotoxicity of sodium salicylate to the spiral ganglion neurons: GABAA receptor regulates NMDA receptor by Fyn-dependent phosphorylation

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Abstract

The purpose of this study was to observe the regulatory effects of GABAA (γ-aminobutyric acid A) receptor on the N-methyl-d-aspartate (NMDA) receptor during excitotoxicity in spiral ganglion neurons in the rat cochlea induced by sodium salicylate (SS). Western blot illustrated SS decreased the expression of NMDA receptor 2B subunit (NR2B) surface protein through affecting GABAA receptor, but the total protein content did not significantly change. Y1472 and S1480 are important phosphorylation sites in NR2B, SS downregulated the Fyn-dependent phosphorylation of Y1472 in a manner not related to the CK2 (Casein Kinase 2) dependent phosphorylation of S1480, thus regulating the surface distribution and internalization of NMDA receptor through GABAA receptor. These results suggest that the modified pattern of dynamic balance between excitation and inhibition by coactivation of the GABAA receptor can attenuate the excitatory NMDA receptor under the action of SS, via inhibiting the Fyn-dependent phosphorylation of Y1472.

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Abbreviations

Bic:

Bicuculline

GABAA :

Receptor agonist

CK2:

Casein Kinase 2

GABAAR:

γ-Aminobutyric acid A receptor

Mus:

Muscimol, GABAA receptor antagonist

NMDAR:

N-Methyl-d-aspartate receptor

NR2B:

NMDA receptor 2B subunit

PP2:

4-Amino-5-(4-chlorophenyl)-7-(t-butyl) pyrazolo[3,4-d] pyrimidine

RQ:

Relative quantity

SGNs:

Spiral ganglion neurons

SS:

Sodium salicylate

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (NSFC) (81360157, 81560174). We also thank the help from the Medical Scientific Research Center of Guangxi Medical University, and the Experimental Animal Center of Guangxi Medical University. All procedures performed in studies involving animals were in accordance with the ethical standards of the NSFC guidelines for the care and use of animals, as described in the “Materials and methods” section.

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  1. Peiqiang Liu and Danxue Qin contributed equally to the work.

Authors and Affiliations

  1. Department of Otolaryngology-Head and Neck Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi, China

    Peiqiang Liu, Danxue Qin, Xi Huang, Huiying Chen, Wenhua Ye, Xiaoyu Lin & Jiping Su

  2. Department of Otolaryngology-Head and Neck Surgery, Wuhan No. 1 Hospital, Wuhan, 430022, Hubei, China

    Xi Huang

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  1. Peiqiang Liu
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Liu, P., Qin, D., Huang, X. et al. Neurotoxicity of sodium salicylate to the spiral ganglion neurons: GABAA receptor regulates NMDA receptor by Fyn-dependent phosphorylation. J Comp Physiol A 205, 469–479 (2019). https://doi.org/10.1007/s00359-019-01339-z

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