| Objective: To determine degenerative changes of intelligence,auditory function and age-related expression of MeCP2 protein in the cochlea of the senescence accelerated dementia mouse/prone 8 throughout development.Methods: The learning capacity and memory,auditory thresholds,the morphological changes of the hair cells and the spiral ganglion neurons and age-related expression of MeCP2 protein in the cochlea were studied in SAMP8 mice of 5,7 months. Normal aging senescence accelerated mouse/resistance 1 (SAMR1) mice served as the control groups. The test of learning capacity and memory in mice was undertaken on Y-type electric maze.8 kHz threshold of auditory brain-stem response (ABR) was determined to observe the binaural auditory function changes. Hair cells calculated on the left cochlear outer hair cells in the average loss rate was to observe the morphological changes of cochlea. The immunohistochemical technique was used to observe the expression of MeCP2 protein in the cochlea.Results: 1.The test of intelligence: On the first day of the test,learning abilities(Training times,Error times,total reaction time) of 5 months SAMP8 mice were 8.57±5.97,3.43±1.13,48.47±15.82(s)respectively. On the second day of the test,memory abilities(Training times,Error times,total reaction time) of 5 months SAMP8 mice were 5.14±3.33,2.71±0.76,46.19±11.63 ( s ) respectively. Learning abilities(Training times,Error times,total reaction time) of 7 months SAMP8 mice were 15.3±6.58,5.20±1.03,73.09±22.56(s);Memory abilities(Training times,Error times,total reaction time) of 7 months SAMP8 mice were 11.2±2.39,3.60±0.84,60.05±12.85(s). On the first day of the test,learning abilities(Training times,Error times,total reaction time) of 5 months SAMR1 mice were 7.29±2.29,1.57±0.53,46.87±11.44(s). On the second day of the test,memory abilities(Training times,Error times,total reaction time) of 5 months SAMR1 mice were 3.57±1.51,0.86±0.38,35.16±7.51(s). Learning abilities(Training times,Error times,total reaction time) of 7 months SAMR1 mice were 8.17±2.99,2.83±1.17,52.57±13.79(s). Memory abilities(Training times, Error times,total reaction time) of 7 months SAMR1 mice were 7.67±2.50,1.83±0.75,44.28±11.31(s).The scores showed that in 7 months SAMP8 mice the training times and mistake numbers increased,total reaction time extended as compared with the control group(P<0.05).Compared with 5 months SAMP8 mice,7 months SAMP8 mice showed an age-related significant increase in the training times,mistake numbers and total reaction time(P<0.05).2.Auditory function: The left ears'ABR threshold (dB SPL) of the experimental groups—5,7 months SAMP8 mice were 49.3±3.59,55.1±5.09, and the values of the control groups—5,7 months SAMR1 were 34.5±5.58,46.7±5.47 respectively. The right ears'ABR threshold (dB SPL) of the experimental groups—5,7 months SAMP8 mice were 46.1±3.53,56.3±6.17, and the values of the control groups—5,7 months SAMR1 mice were 37.5±6.72,47.3±2.07 respectively. Compared with the SAMR1 mice, SAMP8 mice of 7 months developed a progressive binaural hearing loss at 8kHz, which showed an age-related significant increase(P<0.01);compared with the SAMP8 mice of 5 months, SAMP8 mice of 7 months developed a progressive binaural hearing loss at 8kHz, which showed an age-related significant increase(P<0.05).3. The outer hair cells changes of cochlea: Compared with the SAMR1 mice, the SAMP8 mice suffered from age-related loss in the outer hair cells at basal gyrus. The average loss rate in the cochlear outer hair cells at basal gyrus in each group was: 5 months SAMP8 mice 2.4±1.73,5 months SAMR1 mice 1.53±1.21,7 months SAMP8 mice 12.8±3.63 and 7 months SAMR1 mice 2.51±2.2 respectively. Compared with the SAMR1 mice, there was severe outer hair cell loss in the SAMP8 mice in 7 months, which showed a significant increase(P<0.01);compared with the SAMP8 mice of 5 months, there was severe outer hair cell loss in the SAMP8 mice in 7 months, which showed a significant increase(P<0.01).4. The observation of MeCP2 immunohistochemical staining: Compared with the SAMR1 mice, the expression level of MeCP2 protein decreases in the SAMP8 mice,cochlea. The optical density(OD) of MeCP2 immunohistochemical staining in the mice,cochlea of each group was: 5 months SAMP8 mice 38.43±12.37,5 months SAMR1 mice 43.11±10.18,7 months SAMP8 mice 27.26±4.61 and 7 months SAMR1 mice 42.23±9.37 respectively. Compared with the SAMR1 mice,the optical density(OD) of MeCP2 immunohistochemical staining in the SAMP8 at 7 month showed a remarkable significant reduction(P<0.01);compared with the SAMP8 mice of 5 months, the optical density(OD) of MeCP2 immunohistochemical staining in the SAMP8 mice at 7 months showed a remarkable significant reduction (P<0.05).The optical density(OD) of MeCP2 immunohistochemical staining in the mice,cochlea spiral ganglion cell of each group was: 5 months SAMP8 mice 35.69±2.36,5 months SAMR1 mice 42.91±5.87,7 months SAMP8 mice 30.26±3.54 and 7 months SAMR1 mice 40.78±4.27 respectively. Compared with the SAMR1 mice,the optical density(OD) of MeCP2 immunohistochemical staining in the mice , cochlea spiral ganglion cell in the SAMP8 at 7 month showed a remarkable significant reduction(P<0.01),so did in the SAMP8 at 5 month(P<0.05) ;compared with the SAMP8 mice of 5 months, the optical density(OD) of MeCP2 immunohistochemical staining in the mice,cochlea spiral ganglion cell in the SAMP8 at 7 months showed a remarkable significant reduction (P<0.05).Conclusions: The results suggested that there were degenerative changes——deficits of learning ability,auditory function descending,hair cells damaging and the expression level of MeCP2 protein decreasing in the SAMP8 mice. And SAMP8 mice whose auditory system degenerates by ages can be used as the animal model that takes research whether there are some connections between aging-related hearing loss and senile dementia or not. |
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