SCN11A gene deletion causes sensorineural hearing loss by impairing the ribbon synapses and auditory nerves

BMC Neuroscience

Shi-Li Zhang¹  Tao Cong²  Fei Ji²  Mian Zu²  Shi-Ming Yang²  Xin Song²  Yue Zhang²  Wei-Wei Guo²  David Z. Z. He³  Wei Sun⁴  Wei-Guo Shi⁵ 

[1] Clinical Hearing Center of Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China;College of Otolaryngology Head and Neck Surgery, Chinese PLA General Hospital, Beijing, China;National Clinical Research Center for Otolaryngologic Diseases, Beijing, China;Key Lab of Hearing Science, Ministry of Education, Beijing, China;Beijing Key Lab of Hearing Impairment for Prevention and Treatment, Beijing, China;Department of Biomedical Sciences, Creighton University School of Medicine, 68178, Omaha, NE, USA;Department of Communicative Disorders and Sciences, Center for Hearing and Deafness, The State University of New York at Buffalo, Buffalo, NY, USA;State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing, China;

关键词: TTX resistant sodium channels;    Expression;    Nav1.9 knockout;    Ribbon synapse;    SGN;    Progressive hearing loss;    Synaptopathy;   

DOI  :  10.1186/s12868-021-00613-8

来源: Springer

【 摘 要 】

BackgroundThe SCN11A gene, encoded Nav1.9 TTX resistant sodium channels, is a main effector in peripheral inflammation related pain in nociceptive neurons. The role of SCN11A gene in the auditory system has not been well characterized. We therefore examined the expression of SCN11A in the murine cochlea, the morphological and physiological features of Nav1.9 knockout (KO) ICR mice.ResultsNav1.9 expression was found in the primary afferent endings beneath the inner hair cells (IHCs). The relative quantitative expression of Nav1.9 mRNA in modiolus of wild-type (WT) mice remains unchanged from P0 to P60. The number of presynaptic CtBP2 puncta in Nav1.9 KO mice was significantly lower than WT. In addition, the number of SGNs in Nav1.9 KO mice was also less than WT in the basal turn, but not in the apical and middle turns. There was no lesion in the somas and stereocilia of hair cells in Nav1.9 KO mice. Furthermore, Nav1.9 KO mice showed higher and progressive elevated ABR threshold at 16 kHz, and a significant increase in CAP thresholds.ConclusionsThese data suggest a role of Nav1.9 in regulating the function of ribbon synapses and the auditory nerves. The impairment induced by Nav1.9 gene deletion mimics the characters of cochlear synaptopathy.

【 授权许可】

CC BY