Mitochondrial DNA Deletions In Guinea Pigs Associated With Age-related Hearing Loss(presbycusis)

Objective There is no report about mtDNA deletions in guinea pigs, although it is a very ideal animal model in otology research. So to establish the animal model in mtDNA deletions of guinea pigs, we detected the position and the size of mtDNA deletions in guinea pigs. Furthermore, we found the relationship between the rate of mtDNA deletions and the hearing loss in aged guinea pigs. Then our study may contribute to the gene research and therapy about presbycusis.Methods â‘  Tested the hearing threshold of guinea pig by ABR.Firstly the animals were divided in two groups: A. 22 young guinea pigs (2⁴ months); B. 22 aged ones (>24 months). Furthermore the aged group was subdivided in two groups by the threshold: (B₁) normal hearing group; (B₂) hearing impairment group. â‘¡ The level of the blood SOD and MDA in all 44 guinea pigs were measured. â‘¢ By referring to the common law of mtDNA deletions in humans and rats, we searched the possible mtDNA deletions location of guinea pigs with the computer software, and designedcorresponding primers. Total DNA were extracted from cochlear Cortis, auditory nerves and brain tissues and were examined by PCR and DNA sequencing, then we found out the location and the size of mtDNA deletion in guinea-pigs as well as the deletion rates in aged guinea-pigs. ? The cochlear Cortis's tissues, auditory nervours tissues, brain tissues and blood were harvested and the total DNA was extracted. The presence of mtDNA4568 deletion was analyzed by PCR.Results ? There was signifient difference in group A and B; sowas the group Bi (6 normal hearing guinea pigs) and B2(16 hearing impairment guinea pigs ). There was no signifient difference in group A and Bi. (2) The level of blood SOD and MDA between aged group and young group had significant difference. The decline of SOD and the raise of MDA maybe related to presbycusis. (3) Discover originally that there is 4568 bps deletions of mtDNA between nt8636ⁿtl3203 in guinea-pigs. The mtDNA deletion incidence of aged group was significant higer than that of young control group(p<0.05). @ The incidence of mtDNA deletion in Cortis and auditory nerve tissues with presbycusis(B2) were significant higer than that of aged normal hearing group(Bi)(p<0.05); But there was no significant difference in brains between presbycusis group and aged normal hearing group(p>0.05); Only seldom mtDNA4568 deletion occurred in blood.Conclusions ? Auditory sensitivity was reducted with age and theheaing loss was sensorineural hearing impairment. (2) SOD decreased and MDA increased with aging. Presbycusis might result from the decreased SOD and the increased MDA. (3) There is 4568 bps mtDNA deletionbetween nt8636ⁿtl3203 of guinea-pig; These findings indicated the possibility that mtDNA4568 deletion of guinea pigs may be associated with presbycusis, as well as with aging. ?These findings indicated the possibility that mtDNA4568 deletion in cochlear tissues of guinea-pig may be associated with presbycusis, as well as with aging.