title: Age-related hearing loss: GABA, nicotinic acetylcholine and NMDA receptor expression changes in spiral ganglion neurons of the mouse.
abstract: Age-related hearing loss - presbycusis - is the number one communication disorder and most prevalent neurodegenerative condition of our aged population. Although speech understanding in background noise is quite difficult for those with presbycusis, there are currently no biomedical treatments to prevent, delay or reverse this condition. A better understanding of the cochlear mechanisms underlying presbycusis will help lead to future treatments. Objectives of the present study were to investigate GABAA receptor subunit α1, nicotinic acetylcholine (nACh) receptor subunit β2, and N-methyl-d-aspartate (NMDA) receptor subunit NR1 mRNA and protein expression changes in spiral ganglion neurons (SGN) of the CBA/CaJ mouse cochlea, that occur in age-related hearing loss, utilizing quantitative immunohistochemistry and semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) techniques. We found that auditory brainstem response (ABR) thresholds shifted over 40dB from 3 to 48kHz in old mice compared to young adults. DPOAE thresholds also shifted over 40dB from 6 to 49kHz in old mice, and their amplitudes were significantly decreased or absent in the same frequency range. SGN density decreased with age in basal, middle and apical turns, and SGN density of the basal turn declined the most. A positive correlation was observed between SGN density and ABR wave 1amplitude. mRNA and protein expression of GABAAR α1 and AChR β2 decreased with age in SGNs in the old mouse cochlea. mRNA and protein expression of NMDAR NR1 increased with age in SGNs of the old mice. These findings demonstrate that there are functionally-relevant age-related changes of GABAAR, nAChR, NMDAR expression in CBA mouse SGNs reflecting their degeneration, which may be related to functional changes in cochlear synaptic transmission with age, suggesting biological mechanisms for peripheral age-related hearing loss.
authors: Department of Otolaryngology Head and Neck Surgery, First Affiliated Hospital, Guangxi Medical University, 6 Shuangyong Road, Nanning, Guangxi, 530021, China; Department Chemical and Biomedical Engineering, University of South Florida, Tampa, FL 33620, United States; Global Center for Hearing and Speech Research, University of South Florida, Tampa, FL 33620, United States. Electronic address: xiaolan@usf.edu.
authors: X
authors: X
authors: Tang
authors: Department Chemical and Biomedical Engineering, University of South Florida, Tampa, FL 33620, United States; Global Center for Hearing and Speech Research, University of South Florida, Tampa, FL 33620, United States. Electronic address: xiaoxiazhu@usf.edu.
authors: X
authors: X
authors: Zhu
authors: Department Communication Sciences & Disorders, University of South Florida, Tampa, FL 33620, United States; Global Center for Hearing and Speech Research, University of South Florida, Tampa, FL 33620, United States. Electronic address: ding1@usf.edu.
authors: B
authors: B
authors: Ding
authors: Department Chemical and Biomedical Engineering, University of South Florida, Tampa, FL 33620, United States; Department Communication Sciences & Disorders, University of South Florida, Tampa, FL 33620, United States; Global Center for Hearing and Speech Research, University of South Florida, Tampa, FL 33620, United States. Electronic address: jwalton1@usf.edu.
authors: J P
authors: JP
authors: Walton
authors: Department Chemical and Biomedical Engineering, University of South Florida, Tampa, FL 33620, United States; Department Communication Sciences & Disorders, University of South Florida, Tampa, FL 33620, United States; Global Center for Hearing and Speech Research, University of South Florida, Tampa, FL 33620, United States. Electronic address: rfrisina@usf.edu.
authors: R D
authors: RD
authors: Frisina
authors: Department of Otolaryngology Head and Neck Surgery, First Affiliated Hospital, Guangxi Medical University, 6 Shuangyong Road, Nanning, Guangxi, 530021, China. Electronic address: jipingsu@yahoo.com.
authors: J
authors: J
authors: Su
mesh_terms: D000161:Acoustic Stimulation; D000375:Aging / Q000502:physiology*; D000704:Analysis of Variance; D000818:Animals; D003051:Cochlea / Q000033:anatomy & histology / Q000502:physiology; D016057:Evoked Potentials, Auditory, Brain Stem / Q000502:physiology; D051379:Mice; D008808:Mice, Inbred CBA; D009474:Neurons / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011963:Receptors, GABA-A / Q000235:genetics / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism*; D011978:Receptors, Nicotinic / Q000235:genetics / Q000378:metabolism*; D013136:Spiral Ganglion / Q000166:cytology*
chemical_list: D012333:RNA, Messenger; D011963:Receptors, GABA-A; D016194:Receptors, N-Methyl-D-Aspartate; D011978:Receptors, Nicotinic; C409466:NR1 NMDA receptor
keywords: ABR; DPOAE; EDTA; H&E; IC; N-methyl-d-aspartate receptor; NMDAR; OHC; PBS; SGN; TDT; Tucker-Davis technologies; aging; auditory brainstem response; cochlea; distortion product otoacoustic emissions; ethylenediaminetetraacetic acid; gene expression; hearing loss; hematoxylin and eosin; inferior colliculus; nACh; nicotinic acetylcholine; outer hair cells; phosphate-buffered saline; protein expression; spiral ganglion neuron; spiral ganglion neurons