Behavioral consequences of ovarian atrophy and estrogen replacement in the APPswe mouse

Golub, Mari S.; Germann, Stacey L.; Mercer, Mary; Gordon, Marcia N.; Morgan, David G.; Mayer, Loretta P.; Hoyer, Patricia B.

doi:10.1016/j.neurobiolaging.2007.03.015

« Previous Next »Neurobiology of Aging
Volume 29, Issue 10 , Pages 1512-1523, October 2008

Behavioral consequences of ovarian atrophy and estrogen replacement in the APPswe mouse

Mari S. Golub
- Murine Behavioral Assessment Laboratory, University of California, One Shields Avenue, Davis, CA 95616, United States
- Department of Environmental Toxicology, University of California, Davis, CA, United States
- Corresponding author at: California National Primate Research Center, Hutchison and Road 98, Davis, CA 95616, United States. Tel.: +1 530 752 5119; fax: +1 530 752 2880.
Stacey L. Germann
- Murine Behavioral Assessment Laboratory, University of California, One Shields Avenue, Davis, CA 95616, United States
Mary Mercer
- Department of Pharmacology and Molecular Therapeutics, University of South Florida, United States
Marcia N. Gordon
- Department of Pharmacology and Molecular Therapeutics, University of South Florida, United States
David G. Morgan
- Department of Pharmacology and Molecular Therapeutics, University of South Florida, United States
Loretta P. Mayer
- Department of Biological Sciences, Northern Arizona University, United States
Patricia B. Hoyer
- Department of Physiology, University of Arizona, AZ, United States

Received 26 August 2006; received in revised form 9 January 2007; accepted 12 March 2007. published online 25 April 2007.

Abstract

Cognitive performance was evaluated in a longitudinal study of APPswe2576 transgenic mice (APP) and a wildtype (WT) comparison group. Subgroups of the APP mice were treated with the ovarian toxicant 4-vinylcyclo-hexene diepoxide (VCD) at 60–75 days of age to induce ovarian atrophy and/or given estrogen (estradiol, 4μg/day) continuously by pellet from 76 days of age. APP mice had a generally poorer radial maze performance than WT at 4.5, 7.5, 10.5 and 15 months of age. In separate tests, APP mice had a slight motor impairment, higher incidence of homecage stereotypy, hyperactivity in an open field and reduced object exploration relative to the WT group. Ovarian atrophy led to better maze performance at 7.5 months. The effect of estrogen on maze performance with aging could not be effectively evaluated due to poor survival (30%) of these mice. No effects of ovarian atrophy or estrogen treatment were identified for amyloid-beta accumulation or plaque formation at 15 months. Long-term longitudinal studies in animal models are needed to explore the consequences of menopause and hormone replacement on Alzheimer's disease, but they are complicated by considerations of survival, pre-aging deficits, testing experience and selection of appropriate estrogen treatment levels.