Amyloid Precursor Protein (APP) mRNA Level is Higher in the Old Mouse Cerebral Cortex and is Regulated by Sex Steroids |
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Authors: | Thamil Mani Sivanandam M K Thakur |
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Institution: | (1) Biochemistry and Molecular Biology Laboratory, Department of Zoology, Banaras Hindu University, Varanasi, 221005, India; |
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Abstract: | Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by the accumulation of amyloid beta peptides, which
are produced by the proteolytic cleavage of amyloid precursor protein (APP). As the incidence of AD is higher in females and
sex steroids are implicated in this disease, we have examined the effect of sex steroids (testosterone and 17β-estradiol)
on the expression of APP mRNA and protein in the cerebral cortex of adult and old mice of both sexes. Northern blot analysis
detected APP mRNA as a single 3.5-kb band and its level is increased in old as compared to adult. Following gonadectomy, its
level was upregulated in female mice but downregulated in male mice. Supplementation with testosterone or estradiol decreased
its levels in female mice of both ages. Testosterone supplementation increased the mRNA levels in both adult and old male
mice. Estrogen supplementation decreased its level in adult but increased in old male mice. Western blot analysis detected
APP specific bands ranging from 95 to 125 kD. The level of 95 kDa band representing APP695 protein showed difference in levels
with age or hormone treatment. These results provide evidence for increase in APP mRNA level in the cerebral cortex of old
mice and its regulation by sex steroids during aging. |
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