title: Loudness perception affected by early age hearing loss.
abstract: Tinnitus and hyperacusis, commonly seen in adults, are also reported in children. Although clinical studies found children with tinnitus and hyperacusis often suffered from recurrent otitis media, there is no direct study on how temporary hearing loss in the early age affects the sound loudness perception. In this study, sound loudness changes in rats affected by perforation of the tympanic membranes (TM) have been studied using an operant conditioning based behavioral task. We detected significant increases of sound loudness and susceptibility to audiogenic seizures (AGS) in rats with bilateral TM damage at postnatal 16 days. As increase to sound sensitivity is commonly seen in hyperacusis and tinnitus patients, these results suggest that early age hearing loss is a high risk factor to induce tinnitus and hyperacusis in children. In the TM damaged rats, we also detected a reduced expression of GABA receptor δ and α6 subunits in the inferior colliculus (IC) compared to the controls. Treatment of vigabatrin (60 mg/kg/day, 7-14 days), an anti-seizure drug that inhibits the catabolism of GABA, not only blocked AGS, but also significantly attenuated the loudness response. Administration of vigabatrin following the early age TM damage could even prevent rats from developing AGS. These results suggest that TM damage at an early age may cause a permanent reduction of GABA tonic inhibition which is critical towards the maintenance of normal loudness processing of the IC. Increasing GABA concentration during the critical period may alleviate the impairment in the brain induced by early age hearing loss.
authors.affiliation: Center for Hearing & Deafness, Department of Communicative Disorders and Sciences, State University of New York at Buffalo, 3435 Main Street, Buffalo, NY 14214, USA. Electronic address: weisun@buffalo.edu.
authors.forename: Wei
authors.initials: W
authors.lastname: Sun
authors.affiliation: Department of Pharmacology and Toxicology, State University of New York at Buffalo, 3435 Main Street, Buffalo, NY 14214, USA; Department of Biochemistry and Molecular Biology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu 610041, PR China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Fu
authors.affiliation: Center for Hearing & Deafness, Department of Communicative Disorders and Sciences, State University of New York at Buffalo, 3435 Main Street, Buffalo, NY 14214, USA; Department of Otolaryngology, Chinese PLA General Hospital, 28 Fuxing Road, Beijing 100853, PR China.
authors.forename: Chao
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Center for Hearing & Deafness, Department of Communicative Disorders and Sciences, State University of New York at Buffalo, 3435 Main Street, Buffalo, NY 14214, USA.
authors.forename: Senthilvelan
authors.initials: S
authors.lastname: Manohar
authors.affiliation: Center for Hearing & Deafness, Department of Communicative Disorders and Sciences, State University of New York at Buffalo, 3435 Main Street, Buffalo, NY 14214, USA.
authors.forename: Anand
authors.initials: A
authors.lastname: Kumaraguru
authors.affiliation: Department of Pharmacology and Toxicology, State University of New York at Buffalo, 3435 Main Street, Buffalo, NY 14214, USA.
authors.forename: Ji
authors.initials: J
authors.lastname: Li
mesh_terms: D000161:Acoustic Stimulation; D000367:Age Factors; D000818:Animals; D001522:Behavior, Animal; D003216:Conditioning, Operant; D004195:Disease Models, Animal; D020195:Epilepsy, Reflex / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control / Q000523:psychology; D018682:GABA Agents / Q000494:pharmacology; D012001:Hyperacusis / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology / Q000523:psychology; D007245:Inferior Colliculi / Q000378:metabolism / Q000503:physiopathology; D008144:Loudness Perception; D009433:Neural Inhibition; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism; D018058:Tympanic Membrane Perforation / Q000150:complications; D020888:Vigabatrin / Q000494:pharmacology
chemical_list: D018682:GABA Agents; C546173:Gabra6 protein, rat; C000592156:Gabrd protein, rat; D011963:Receptors, GABA-A; D020888:Vigabatrin