Behavioral consequences of ovarian atrophy and estrogen replacement in the APPswe mouse.
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, 4 microg/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.
Golub
Mari S
MS
Murine Behavioral Assessment Laboratory, University of California, One Shields Avenue, Davis, CA 95616, United States. msgolub@ucdavis.edu
Germann
Stacey L
SL
Mercer
Mary
M
Gordon
Marcia N
MN
Morgan
David G
DG
Mayer
Loretta P
LP
Hoyer
Patricia B
PB
D000375:Aging / Q000378:metabolism*; D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001284:Atrophy / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D003072:Cognition Disorders / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D015914:Estrogen Replacement Therapy; D004967:Estrogens / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D008137:Longitudinal Studies; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D010053:Ovary / Q000187:drug effects / Q000378:metabolism; D017698:Postmenopause / Q000378:metabolism*; D015203:Reproducibility of Results
D016564:Amyloid beta-Protein Precursor; D004967:Estrogens; D018696:Neuroprotective Agents