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Effects of long-term treatment with estrogen and medroxyprogesterone acetate on synapse number in the medial prefrontal cortex of aged female rats

Chisholm, Nioka C. MA; Juraska, Janice M. PhD

doi: 10.1097/gme.0b013e31824d1fc4
Original Articles

Objective: The present study investigated the effects of long-term hormone treatment, including the most commonly prescribed progestin, medroxyprogesterone acetate, during aging on synaptophysin-labeled boutons, a marker of synapses, in the medial prefrontal cortex (mPFC) of rats.

Methods: Female Long Evans hooded rats were ovariectomized at middle age (12-13 mo) and were placed in one of four groups: no replacement (n = 5), 17β-estradiol alone (n = 6), estradiol and progesterone (n = 7), or estradiol and medroxyprogesterone acetate (n = 4). Estradiol was administered in the drinking water and progestogens were administered via subcutaneous pellets that were replaced every 90 days. After 7 months of hormone replacement, the animals were euthanized, and the brains were stained for synaptophysin, a membrane component of synaptic vesicles. The density of synaptophysin-labeled boutons was quantified in the mPFC using unbiased stereology and multiplied by the volume of the mPFC to obtain the total number.

Results: Animals receiving estradiol and medroxyprogesterone acetate had significantly more synaptophysin-labeled boutons in the mPFC than did animals not receiving replacement (P < 0.03) and those receiving estradiol and progesterone (P < 0.02). In addition, there was a nonsignificant trend for animals receiving estradiol alone to have more synapses than those receiving estradiol and progesterone.

Conclusions: This study is the first to examine the effects of estradiol and medroxyprogesterone acetate during rat aging on cortical synaptic number. Estradiol with medroxyprogesterone acetate, but not progesterone, resulted in a greater number of synapses in the mPFC during aging than did no replacement.

Middle-aged female rats received long-term treatment with several types of hormone therapy. The group that received estrogen with medroxyprogesterone had a greater number of synapses in the medial prefrontal cortex than did the group receiving no treatment.

From the 1Departments of Psychology and 2Neuroscience Program, University of Illinois at Urbana-Champaign, Champaign, IL.

Received November 9, 2011; revised and accepted January 26, 2012.

Funding/support: This study was supported by NIH AG 022499.

Financial disclosure/conflicts of interest: None reported.

Author Nioka C. Chisholm was previously published as Nioka C. Lowry.

Address correspondence to: Janice M. Juraska, PhD, Department of Psychology, University of Illinois, 603 E. Daniel Street, Champaign, IL 61820. E-mail: jjuraska@illinois.edu

© 2012 by The North American Menopause Society.