Oral Presentation The International Congress of Neuroendocrinology 2014

Reproductive experience alters the effects of estrogens on hippocampus-dependent working and reference memory and neurogenesis in middle-aged female rats. (#38)

Cindy K Barha 1 , Stephanie E Lieblich 2 , Carmen Chow 2 , Liisa A Galea 2
  1. Simon Fraser University, Burnaby, BC, Canada
  2. Psychology, University of British Columbia, Vancouver, BC, Canada

Reproductive experience alters hippocampal structure and function with effects seen across the lifespan. Specifically, parity has been associated with enhanced hippocampus-dependent spatial memory and altered hippocampal neurogenesis in female rats. Recently, we showed that different estrogens promote cell proliferation in the hippocampus of multiparous, but not nulliparous, middle-aged female rats. Estradiol is the more common estrogen in young women, while estrone is more common in older women. The most commonly prescribed hormone replacement therapy (HRT) consists primarily of estrone, and does not have as many cognitive enhancing benefits as HRTs that consist primarily of estradiol. The aim of the present study was to determine the chronic effects of estrogens (17β-estradiol, 17α-estradiol, estrone) and previous reproductive experience on hippocampus-dependent memory and neurogenesis. Middle-aged multiparous and nulliparous female rats were given daily injections of vehicle or one of the three estrogens (10µg) for 20 days. Rats were trained on working and reference memory versions of the Morris water maze, given a probe trial, and perfused in order to examine production of new neurons. Multiparous rats outperformed nulliparous rats in the working memory task, while nulliparous rats outperformed multiparous rats on the reference memory task. Nulliparous rats had more 21-day old neurons in the dentate gyrus than multiparous rats. Furthermore, preliminary findings suggest that all estrogens impaired working memory in multiparous rats, while estrone enhanced working memory in nulliparous rats. 17β-estradiol enhanced reference memory in multiparous rats, while all estrogens impaired reference memory in nulliparous rats. Furthermore, 17β-estradiol enhanced, while estrone and 17α-estradiol impaired retention of reference memory only in multiparous rats. Findings from this study advance our understanding of how different estrogens mediate cognition in older rats, and may ultimately lead to the development and tailoring of new therapeutic advances in the treatment of symptoms associated with menopause in women.