الفهرس 
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Abstract
Age-related hearing loss (ARHL) is the most prevalent sensory deficit in the elderly. The increasing life expectancy of the human population has rendered the effects of aging more prominent, and it is important to improve our understanding of ARHL.
Dehydroepiandrosterone (DHEA) is a metabolic intermediate in the biosynthesis of estrogens and androgens. It is proven to have central effects and anti-aging properties.
This work aimed to investigate the effect of administration of DHEA on the age-related changes of primary auditory cortex in senile male albino rats.
10 adult male rats aged 4-6 months (200-250 gm) and 30 senile male albino rats aged 20-24 months (350-500 gm) were used in this study. They were divided into 4 groups (10 rats in each group) as follows: group I (adult group): 10 rats received no medications for 8 weeks. group II (senile group):10 rats received no medication for 8 weeks. group III (senile group treated with Dimethy Sulfoxide (DMSO)): 10 rats received 1ml/kg/B.W. of DMSO once daily by oral gavage for 8 weeks. group IV (senile group treated with DHEA):10 rats received 20mg/kg/B.W. of DHEA dissolved in 1ml/kg/B.W of DMSO once daily by oral gavage for 8 weeks.
Blood samples were collected by retro orbital puncture then serum was separated by centrifugation and was used for estimation of DHEA level at the start and at the end of the experiment.
At the end of experiment, rats were anesthetized and sacrificed. The skulls were opened, the brains were dissected out and the caudal third of both cerebral hemispheres were cut by coronal section. Some specimens were fixed and processed to prepare paraffin blocks. Sections of 5µ thick were cut, stained with H&E and with silver stain.
Some paraffin sections were immunostained to detect glial fibrillary acidic protein (GFAP) in astrocytes.
Other specimens were fixed in 3% phosphate buffered glutraladehyde and processed to cut semithin sections at 1µm thickness. Sections were stained with 1% toluidine blue stain.
All stained sections were examined with the light microscope.
Morphometric study was performed using image analyzer. The auditory cortical thickness in µm, the count of pyramidal cells and the count of GFAP positive astrocytes were measured. Results were subjected to statistical analysis (ANOVA) and data was represented in tables and bar charts.
Examination of the H&E-stained and semithin sections of the primary auditory area of the cerebral cortex of adult male albino rats showed that it was differentiated into six layers that could be easily identified with vertical arrangement of cells perpendicular to the surface of the cortex. The pyramidal cell was characterized by a large, rounded nucleus with prominent nucleoli. The cytoplasm was basophilic extending along the apical dendrites which were thick and directed towards the surface. Granular cells looked rounded and had pale vesicular rounded nuclei with an outer rim of basophilic cytoplasm. Few neuroglia appeared free in the neuropil.
Examination of the H&E-stained sections and semithin sections of the senile group revealed shrunken pyramidal cells with deeply stained nuclei. Appearance of large unstained peri-cellular spaces surrounding these cells were detected. Numerous microglia were also observed. In addition, wide areas of vacuolated neuropil were noticed. However, in DHEA group, multiple pyramidal and granular cells appeared normal with persistence of few shrunken cells. Apperrantly decreased number of neuroglia cells were seen compared to the senile group.
Sections of DMSO group gave the same histopathological picture of the senile group.
Examination of silver-stained sections of the adult group showed well-organized cell arrangement and high density of nerve fibers in the cortical layers. Apical dendrites of pyramidal cells were clearly defined, being long, thick and directed towards the surface of the cortex. Collaterals arising from the stem of the apical dendrite were seen. The Basal dendrites were short, tapering and branching. While Examination of the silver-stained sections of the senile group revealed apparent decrease in nerve fibers density. Apical dendrites of pyramidal cells were thin and shrunken. Moreover, examination of sections of the DHEA group showed apparent increased density of nerve fibers. The apical process of pyramidal cells appeared relatively long.
Immunohistochemical staining for GFAP in the adult group showed mild positive GFAP staining in the cytoplasm of astrocytes and their processes. Astrocytes appeared small with few short, thin processes. While immunohistochemical staining for GFAP in the senile group showed strong positive GFAP staining in the cytoplasm of abundant astrocytes with multiple thickened processes compared to the adult group. Immunohistochemical staining for GFAP of DHEA group showed GFAP moderate positive staining in the cytoplasm of astrocytes and their processes compared to the senile group.
The morphometric study of the current study revealed statistically significant decrease in the mean cortical thickness in the senile group compared to the adult group and statistically significant increase in the DHEA group compared to the senile group was observed.
There was highly statistically significant decrease in the mean count of pyramidal cells in the senile group compared to the adult group and statistically significant increase in the DHEA group compared to the senile group.
Also, there was highly statistically significant increase in the mean count of GFAP positive astrocytes in the senile group compared to the adult group and significant decrease of these cells in the DHEA group compared to the senile group.
There was highly statistically significant decrease in the mean DHEA level in the senile group compared to the adult group and highly statistically significant increase of this level in the DHEA group compared to the senile group.
Our study was correlated with other studies and it was concluded that DHEA can slow down age related changes in the primary auditory area of the senile rats’ cerebral cortex. Hence, it is recommended to include DHEA as a promising therapeutic strategy to attenuate ARHL in aged individuals.