PS1 expression is downregulated by gonadal steroids in adult mouse brain.
Mutations in presenilin (PS) 1 and PS2 genes are associated with early onset (< or =65 years) of Alzheimer's disease (AD). PS1 is involved in gamma-secretase mediated cleavage of beta-amyloid precursor protein (APP), but its regulation is poorly understood. Sex steroids influence APP cleavage pathways resulting in reduced burden of both intra- and extra-cellular nonamyloidogenic products. As gonadal hormones are implicated in AD and their levels change with age, we have analyzed the effect of 17beta-estradiol and testosterone on PS1 expression in the cerebral cortex of adult and old AKR mice of both sexes. Northern and Western-blot analysis revealed that PS1 mRNA and protein expression followed similar pattern of regulation. PS1 expression was downregulated by 17 beta-estradiol and testosterone in the cerebral cortex of females and adult male, but upregulated in old male mice. Such sex-dependent regulation of PS1 expression during aging by gonadal steroids might account for the PS-related brain functions.
Ghosh
Soumi
S
Biochemistry & Molecular Biology Laboratory, Department of Zoology, Banaras Hindu University, Varanasi 221005, India.
Thakur
Mahendra Kumar
MK
D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D001923:Brain Chemistry / Q000187:drug effects*; D002540:Cerebral Cortex / Q000254:growth & development / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D012739:Gonadal Steroid Hormones / Q000494:pharmacology*; D017403:In Situ Hybridization; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis / Q000302:isolation & purification; D051379:Mice; D008806:Mice, Inbred AKR; D053764:Presenilin-1 / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000302:isolation & purification; D012727:Sex Characteristics; D013739:Testosterone / Q000494:pharmacology
D012739:Gonadal Steroid Hormones; D008565:Membrane Proteins; D053764:Presenilin-1; D012333:RNA, Messenger; D013739:Testosterone; D004958:Estradiol
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