title: Puerarin alleviates noise-induced hearing loss via affecting PKCγ and GABAB receptor expression.
abstract: Noise-induced hearing loss (NIHL) often results from prolonged exposure to high levels of noise. Our previous study revealed that during the development of NIHL, the expression of protein kinase C γ subunit (PKCγ) and GABAB receptor (GABABR) was changed within the cochlear nuclear complex (CNC), suggesting that these molecules might be the potential targets for the treatment of NIHL. As an extending study, here we focused on puerarin, a major isoflavonoid extracted from Pueraria lobota, which has been used in the treatment of cardiovascular and cerebrovascular diseases, and investigated whether it could protect against NIHL by acting on PKCγ and GABABR. Transgenic GAD67-GFP knock-in mice were subjected to the NIHL model and their auditory functions were evaluated by the auditory brainstem response thresholds and distortion product oto-acoustic emission signals. Our results showed that 200mg/kg puerarin treatment ameliorated the thresholds of auditory brainstem response of NIHL mice significantly. Triple immunofluorescence staining and electron microscopy results revealed that GFP-positive neurons in the superficial layers of CNC expressed both PKCγ and GABABR1, and GAD67-positive terminals contacted PKCγ- or GABABR1-positive neurons. Immunoblotting and RT-PCR results showed that NIHL increased the expression of PKCγ but decreased that of GABABR1 and GABABR2 at both protein and mRNA levels in the CNC. Puerarin significantly attenuated the increased expression of PKCγ but elevated the reduced expression of GABABR1 and GABABR2 after noise exposure. Thus, we provided the first evidence that puerarin ameliorated the auditory functions of NIHL mice, and this effect may be due to its ability to regulate the expression of PKCγ and GABABR.
authors.affiliation: Department of Anatomy, Histology and Embryology, K.K. Leung Brain Research Centre, Fourth Military Medical University, Xi'an 710032, China; Department of Otolaryngology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Qu
authors.affiliation: Department of Anatomy, Histology and Embryology, K.K. Leung Brain Research Centre, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Yong-Hui
authors.initials: YH
authors.lastname: Liao
authors.affiliation: Department of Anatomy, Histology and Embryology, K.K. Leung Brain Research Centre, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Zhen-Zhen
authors.initials: ZZ
authors.lastname: Kou
authors.affiliation: Department of Anatomy, Histology and Embryology, K.K. Leung Brain Research Centre, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Yan-Yan
authors.initials: YY
authors.lastname: Wei
authors.affiliation: Department of Anatomy, Histology and Embryology, K.K. Leung Brain Research Centre, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Anatomy, Histology and Embryology, K.K. Leung Brain Research Centre, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Genetic and Behavioral Neuroscience, Gunma University Graduate School of Medicine, Maebashi 371-8511, Japan.
authors.forename: Yuchio
authors.initials: Y
authors.lastname: Yanagawa
authors.affiliation: Department of Anatomy, Histology and Embryology, K.K. Leung Brain Research Centre, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Sheng-Xi
authors.initials: SX
authors.lastname: Wu
authors.affiliation: Department of Neurology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China. Electronic address: biomidas@fmmu.edu.cn.
authors.forename: Ming
authors.initials: M
authors.lastname: Shi
authors.affiliation: Department of Anatomy, Histology and Embryology, K.K. Leung Brain Research Centre, Fourth Military Medical University, Xi'an 710032, China. Electronic address: deptanat@fmmu.edu.cn.
authors.forename: Yun-Qing
authors.initials: YQ
authors.lastname: Li
mesh_terms: D000818:Animals; D015153:Blotting, Western; D004195:Disease Models, Animal; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005968:Glutamate Decarboxylase / Q000378:metabolism; D006317:Hearing Loss, Noise-Induced / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D007529:Isoflavones / Q000627:therapeutic use*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D018080:Receptors, GABA-B / Q000235:genetics / Q000378:metabolism*; D014665:Vasodilator Agents / Q000627:therapeutic use*
chemical_list: D005904:Glial Fibrillary Acidic Protein; D007529:Isoflavones; D010446:Peptide Fragments; D012333:RNA, Messenger; D018080:Receptors, GABA-B; D014665:Vasodilator Agents; C087857:protein kinase C gamma; D011493:Protein Kinase C; D005968:Glutamate Decarboxylase; C505593:glutamic acid decarboxylase 65 (524-543), mouse; C033607:puerarin
keywords: Cochlear nucleus complex; GABA(B) receptor; Noise-induced hearing loss; PKCγ; Puerarin; Transgenic mice