title: PS1 expression is downregulated by gonadal steroids in adult mouse brain.
abstract: 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.
authors: Biochemistry & Molecular Biology Laboratory, Department of Zoology, Banaras Hindu University, Varanasi 221005, India.
authors: Soumi
authors: S
authors: Ghosh
authors: Mahendra Kumar
authors: MK
authors: Thakur
mesh_terms: 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
chemical_list: D012739:Gonadal Steroid Hormones; D008565:Membrane Proteins; D053764:Presenilin-1; D012333:RNA, Messenger; D013739:Testosterone; D004958:Estradiol
references: Curr Opin Neurobiol. 2004 Jun;14(3):379-83
references: 15194119
references: Trends Genet. 2007 Mar;23(3):140-50
references: 17280736
references: J Biol Chem. 1997 Sep 19;272(38):23489-97
references: 9295283
references: Endocrinology. 2002 Jun;143(6):2093-105
references: 12021174
references: Anal Biochem. 1985 Oct;150(1):76-85
references: 3843705
references: J Neurosci. 1996 Dec 1;16(23):7513-25
references: 8922407
references: J Biol Chem. 2004 May 7;279(19):20539-45
references: 14871891
references: Neurobiol Aging. 2006 Jun;27(6):880-7
references: 15916834
references: Neurochem Int. 2007 Jan;50(2):314-21
references: 17113197
references: Nat Med. 2006 Dec;12(12):1390-6
references: 17115048
references: Proc Natl Acad Sci U S A. 2006 Feb 7;103(6):1941-6
references: 16449386
references: Anal Biochem. 1987 Apr;162(1):156-9
references: 2440339
references: Nat Med. 1998 Apr;4(4):447-51
references: 9546791
references: Eur J Endocrinol. 2004 Oct;151(4):503-10
references: 15476452
references: J Biol Chem. 2004 Oct 22;279(43):44945-54
references: 15322084
references: J Neurosci. 2004 Jun 9;24(23):5315-21
references: 15190103
references: Mol Cell Biochem. 2000 Jan;203(1-2):95-101
references: 10724337
references: Neurosci Lett. 2005 Jun 10-17;381(1-2):154-7
references: 15882808