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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:

© 2012 by The North American Menopause Society.