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Effects of chronic estradiol treatment on acquisition and reacquisition of working memory and cell proliferation in the dentate gyrus

University of British Columbia

Beyond its role in reproduction, estrogen exerts profound effects on cognition and behaviour as well as influencing the structural and electrophysiological properties of the brain. The present studies investigate the effect of chronic estradiol treatment on acquisition and reacquisition of the prefrontal cortex-dependent delayed non-matched to position T-maze task and on cell proliferation in the dentate gyrus of adult female rats. Experiment 1 investigates the effect of estradiol on non-spatial working memory during the T-maze task. Ovariectomized (OVX) female rats were injected for 21d with estradiol benzoate (0.3, 5 or 10 μg/0.1 ml sesame oil) or vehicle (sesame oil, 0.1 ml). Approximately 2hr after each injection, animals were trained daily on the T-maze with an initial delay of 10s. Following a month with no estradiol treatment animals were injected for 21d with the same initial doses of estradiol and re-trained (reacquisition) at a 40s delay. Days to reach criterion (one error per day for three consecutive days), mean total errors (entries into previously baited arms), errors across blocks (3d per block), change in performance across training (acquisition subtracted from reacquisition), and latency to reach goal arm, were scored. Compared to OVX rats without estrogen administration, a dose of 0.3 of estradiol (low-to-medium physiological) significantly decreased the number of working memory errors during a 10s delay (acquisition), while doses of both 5 μg (high physiological) and 10 μg (supraphysiological) of estradiol significantly increased the number of working memory errors during a 40s delay (reacquisition). Experiment 2 investigated the effect of chronic estradiol treatment on the proliferation of cells in the dentate gyrus of adult female rats. Ovariectomized (OVX) female rats were injected for 21d with estradiol benzoate (0.3, 5 or 10 μg /0.1 ml) or vehicle (sesame oil; 0.1 ml). Four hours after the last hormone injection on day 21 animals were injected i.p. with bromodeoxyuridine (BrdU; 200mg/kg), a thymidine analogue and were perfused 24h later. Stereo logical counts of BrdU-labelled cells and dentate gyrus volume were correlated with serum estradiol levels. Results revealed that regardless of dose, estradiol treatment produced no significant change in the number of BrdU-labelled cells observed relative to vehicle-controls. Similarly, estradiol treatment produced no significant change in the number of pyknotic cells observed across treatment conditions relative to vehicle controls. However, chronic treatment with supraphysiological levels of estradiol (10 μg) significantly increased dentate gyrus volume. There was no significant correlation between serum estradiol levels and number of BrdU-labelled cells, however DG volume correlated positively with serum estradiol dose. These data demonstrate that chronic estradiol has a significant differential effect on acquisition and reacquisition of prefrontal cortex dependent working memory. While chronic estradiol did not significantly affect the number of BrdU-labelled cells, serum estradiol was positively correlated with DG volume.

Thesis/Dissertation

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2009-10-28

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http://hdl.handle.net/2429/14265

Neuroscience

University of British Columbia

UBCV

DSpace