Journal
HORMONES AND BEHAVIOR
Volume 87, Issue -, Pages 96-114Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.yhbeh.2016.10.010
Keywords
Menopause; Aging; VCD; Cognition; Learning; Memory; Hormone; Ovary
Categories
Funding
- National Institute on Aging [AG028084]
- state of Arizona
- ADHS
- Alzheimer's Disease Core Center Pilot grant program
- NIH Initiative for Maximizing Student Development (IMSD) program [R25GM099650]
- More Graduate Education at Mountain States Alliance for Graduate Education
- Professoriate (AGEP) National Science Foundation [HRD-0450137]
- Western Alliance to Expand Student Opportunities Louis Stokes Alliance for Minority Participation Bridge to the Doctorate (WAESO-LSAMP-BD)
- National Science Foundation [HDR-1025879]
- National Institute of Mental Health [F32 MH093145]
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Cognitive changes that occur during mid-life and beyond are linked to both aging and the menopause transition. Studies in women suggest that the age at menopause onset can impact cognitive status later in life; yet, little is known about memory changes that occur during the transitional period to the postmenopausal state. The 4-vinylcydohexene diepoxide (VCD) model simulates transitional menopause in rodents by depleting the immature ovarian follicle reserve and allowing animals to retain their follicle-deplete ovarian tissue, resulting in a profile similar to the majority of perimenopausal women. Here, Vehicle or VCD treatment was administered to ovary-intact adult and middle-aged Fischer-344 rats to assess the trajectory of cognitive change across time with normal aging and aging with transitional menopause via VCD-induced follicular depletion, as well as to evaluate whether age at the onset of follicular depletion plays a role in cognitive outcomes. Animals experiencing the onset of menopause at a younger age exhibited impaired spatial memory early in the transition to a follicle-deplete state. Additionally, at the mid-and post-follicular depletion time points, VCD-induced follicular depletion amplified an age effect on memory. Overall, these findings suggest that age at the onset of menopause is a critical parameter to consider when evaluating learning and memory across the transition to reproductive senescence. From a translational perspective, this study illustrates how age at menopause onset might impact cognition in menopausal women, and provides insight into time points to explore for the window of opportunity for hormone therapy during the menopause transition period. Hormone therapy during this critical juncture might be especially efficacious at attenuating age-and menopause-related cognitive decline, producing healthy brain aging profiles in women who retain their ovaries throughout their lifespan. (C) 2016 Elsevier Inc. All rights reserved.
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