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Effects of progesterone administration and APPswe+PSEN1Deltae9 mutation for cognitive performance of mid-aged mice.
Neurobiol Learn Mem 2008; 89(1):17-26NL

Abstract

Progesterone (P(4)) and its metabolite, 5alpha-pregnan-3alpha-ol-20-one (3alpha,5alpha-THP) have trophic effects and may improve cognitive function. We investigated the role of progestins in a murine model of Alzheimer's Disease (AD) in which transgenic mice co-overexpress a mutant form of amyloid precursor protein (APPswe) and a deletion in presenilin 1 Delta exon 9 (APPswe+PSEN1Deltae9). We hypothesized that: (1) mice with the APPswe+PSEN1Deltae9 mutation would have performance deficits compared to wildtype mice and (2) long-term administration of P(4) would enhance cognitive performance and increase brain progestin levels over placebo. Mice were ovariectomized at 6 months of age and administered placebo or P(4) via subcutaneously implanted pellets. Mice were tested between 9 and 12 months of age for cognitive performance in the object placement, water maze, object recognition, and T-maze tasks and for motor behavior in an activity monitor and then tissues were collected for steroid measurement. P(4) administration increased progestin levels in cortex, diencephalon, midbrain, and cerebellum of wildtype and mutant mice, but increases in 3alpha,5alpha-THP levels in the hippocampus of APPswe+PSEN1Deltae9 mutant mice were attenuated compared to that observed in wildtype mice. APPswe+PSEN1Deltae9 mice showed poorer performance in hippocampus measures (object placement and water maze tasks). In the object recognition and T-maze task, which are mediated by the cortex and hippocampus, P(4) administration improved performance in both wildtype and APPswe+PSEN1Deltae9 mutant mice compared to placebo administration. Thus, APPswe+PSEN1Delta9 mice have deficits in hippocampal performance and capacity to form 3alpha,5alpha-THP in the hippocampus and both wildtype and APPswe+PSEN1Delta9 mice show beneficial effects of P(4) in cortical function and similar capacity to form 3alpha,5alpha-THP in the cortex.

Authors+Show Affiliations

Department of Psychology, The University at Albany-SUNY, Life Sciences Research Building 01058, 1400 Washington Avenue, Albany, NY 12222, USA. cafrye@albany.eduNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

17988898

Citation

Frye, Cheryl A., and Alicia A. Walf. "Effects of Progesterone Administration and APPswe+PSEN1Deltae9 Mutation for Cognitive Performance of Mid-aged Mice." Neurobiology of Learning and Memory, vol. 89, no. 1, 2008, pp. 17-26.
Frye CA, Walf AA. Effects of progesterone administration and APPswe+PSEN1Deltae9 mutation for cognitive performance of mid-aged mice. Neurobiol Learn Mem. 2008;89(1):17-26.
Frye, C. A., & Walf, A. A. (2008). Effects of progesterone administration and APPswe+PSEN1Deltae9 mutation for cognitive performance of mid-aged mice. Neurobiology of Learning and Memory, 89(1), pp. 17-26.
Frye CA, Walf AA. Effects of Progesterone Administration and APPswe+PSEN1Deltae9 Mutation for Cognitive Performance of Mid-aged Mice. Neurobiol Learn Mem. 2008;89(1):17-26. PubMed PMID: 17988898.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of progesterone administration and APPswe+PSEN1Deltae9 mutation for cognitive performance of mid-aged mice. AU - Frye,Cheryl A, AU - Walf,Alicia A, Y1 - 2007/11/07/ PY - 2007/08/10/received PY - 2007/09/14/revised PY - 2007/09/26/accepted PY - 2007/11/9/pubmed PY - 2008/2/22/medline PY - 2007/11/9/entrez SP - 17 EP - 26 JF - Neurobiology of learning and memory JO - Neurobiol Learn Mem VL - 89 IS - 1 N2 - Progesterone (P(4)) and its metabolite, 5alpha-pregnan-3alpha-ol-20-one (3alpha,5alpha-THP) have trophic effects and may improve cognitive function. We investigated the role of progestins in a murine model of Alzheimer's Disease (AD) in which transgenic mice co-overexpress a mutant form of amyloid precursor protein (APPswe) and a deletion in presenilin 1 Delta exon 9 (APPswe+PSEN1Deltae9). We hypothesized that: (1) mice with the APPswe+PSEN1Deltae9 mutation would have performance deficits compared to wildtype mice and (2) long-term administration of P(4) would enhance cognitive performance and increase brain progestin levels over placebo. Mice were ovariectomized at 6 months of age and administered placebo or P(4) via subcutaneously implanted pellets. Mice were tested between 9 and 12 months of age for cognitive performance in the object placement, water maze, object recognition, and T-maze tasks and for motor behavior in an activity monitor and then tissues were collected for steroid measurement. P(4) administration increased progestin levels in cortex, diencephalon, midbrain, and cerebellum of wildtype and mutant mice, but increases in 3alpha,5alpha-THP levels in the hippocampus of APPswe+PSEN1Deltae9 mutant mice were attenuated compared to that observed in wildtype mice. APPswe+PSEN1Deltae9 mice showed poorer performance in hippocampus measures (object placement and water maze tasks). In the object recognition and T-maze task, which are mediated by the cortex and hippocampus, P(4) administration improved performance in both wildtype and APPswe+PSEN1Deltae9 mutant mice compared to placebo administration. Thus, APPswe+PSEN1Delta9 mice have deficits in hippocampal performance and capacity to form 3alpha,5alpha-THP in the hippocampus and both wildtype and APPswe+PSEN1Delta9 mice show beneficial effects of P(4) in cortical function and similar capacity to form 3alpha,5alpha-THP in the cortex. SN - 1074-7427 UR - https://www.unboundmedicine.com/medline/citation/17988898/Effects_of_progesterone_administration_and_APPswe+PSEN1Deltae9_mutation_for_cognitive_performance_of_mid_aged_mice_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1074-7427(07)00161-X DB - PRIME DP - Unbound Medicine ER -