Age-related changes in the central auditory system: comparison of D-galactose-induced aging rats and naturally aging rats.
One of the most common complaints among aging individuals is difficulty in understanding speech in a compromised listening environment, such as when background noise is present. Age-related hearing loss (presbycusis) is associated with both peripheral and central neural processing deficits, as it occurs even in those with only a mild peripheral hearing impairment. The current study was designed to investigate potential causative mechanisms of this impairment by using a rat model in which presbycusis is inducible by administration of D-galactose (D-gal). One group of these rats was injected subcutaneously with 150 mg D-gal daily for 8 weeks, while control animals received vehicle only. These groups were compared to naturally aged rats (24 months) that had received no other treatment. Central auditory function of the three groups was evaluated by measuring the auditory brainstem response (ABR) and middle latency response (MLR). A TaqMan real time PCR assay was used to quantify a 4834-bp deletion in the mitochondrial DNA (mtDNA) of the auditory cortex (AC), inferior colliculus (IC) and cochlear nucleus (CN). We assessed changes in lipid peroxidation levels and apoptosis rates, and examined pathological changes corresponding to D-gal-induced aging and natural aging. Both groups of aged rats exhibited delayed ABR latencies (III, IV, V), MLR Pa latency, and I-IV interpeak latency. Moreover, increased mtDNA 4834 bp deletion rates, lipid peroxidation levels, rates of neuronal apoptosis and neurodegenerative changes in the AC, IC and CN were similar among the D-gal induced and NA rats. However, the threshold of ABR in the D-gal group showed no significant change from the control group. These observations suggest that age-related central auditory dysfunction and its corresponding pathological changes are present in both naturally aging rats and the D-gal mimetic aging model. Oxidative stress, large-scale mtDNA 4834 bp deletion, and apoptosis are likely to be involved in the progressive weakening of the central auditory system associated with the aging process.
Chen
Bei
B
Department of Otolaryngology, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, China.
Zhong
Yi
Y
Peng
Wei
W
Sun
Yu
Y
Kong
Wei-Jia
WJ
D000367:Age Factors; D000375:Aging / Q000187:drug effects* / Q000502:physiology; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects; D001306:Auditory Pathways / Q000187:drug effects / Q000503:physiopathology* / Q000648:ultrastructure; D001483:Base Sequence / Q000187:drug effects; D004272:DNA, Mitochondrial / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects; D005690:Galactose / Q000633:toxicity*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D046529:Microscopy, Electron, Transmission / Q000379:methods; D009474:Neurons / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D011304:Presbycusis / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D017384:Sequence Deletion / Q000187:drug effects
D004272:DNA, Mitochondrial; D005690:Galactose