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Premarin has opposing effects on spatial learning, neural activation, and serum cytokine levels in middle-aged female rats depending on reproductive history Galea, Liisa A. M.; Roes, Meighen Maria; Dimech, Christiana J.; Chow, Carmen; Mahmoud, Rand; Lieblich, Stephanie E.; Duarte-Guterman, Paula

Abstract

Menopause is associated with cognitive decline, and hormone therapies (HT) may improve cognition depending on type, and timing of HT. Previous parity may influence cognition in later life. We investigated how primiparity and long-term ovariectomy influence cognition, neurogenesis, hormones, cytokines, and neuronal activation in middle-aged rats in response to Premarin, an HT. Nulliparous and primiparous rats were sham-ovariectomized or ovariectomized, administered vehicle or Premarin six months later, and all rats were trained in the Morris water maze. Premarin improved spatial learning and memory in nulliparous rats, but impaired early learning in primiparous rats. With training, primiparity increased hippocampal neurogenesis, and Premarin decreased immature neurons, regardless of parity. Moreover, Premarin increased serum tumor necrosis factor (TNF) α and the CXC chemokine ligand 1 (CXCL1) in nulliparous, but not primiparous, trained rats. However, Premarin decreased the expression of the immediate early gene zif268 in the dorsal CA3 region in primiparous rats after training. Thus, primiparity alters how Premarin affects spatial learning, neuronal activation, and serum cytokines. These findings have implications for the treatment of age-associated cognitive decline in women.

Item Metadata

Title
Premarin has opposing effects on spatial learning, neural activation, and serum cytokine levels in middle-aged female rats depending on reproductive history
Creator
Galea, Liisa A. M.; Roes, Meighen Maria; Dimech, Christiana J.; Chow, Carmen; Mahmoud, Rand; Lieblich, Stephanie E.; Duarte-Guterman, Paula
Contributor
Djavad Mowafaghian Centre for Brain Health; University of British Columbia. Graduate Program in Neuroscience
Date Issued
2018
Description
Menopause is associated with cognitive decline, and hormone therapies (HT) may improve cognition depending on type, and timing of HT. Previous parity may influence cognition in later life. We investigated how primiparity and long-term ovariectomy influence cognition, neurogenesis, hormones, cytokines, and neuronal activation in middle-aged rats in response to Premarin, an HT. Nulliparous and primiparous rats were sham-ovariectomized or ovariectomized, administered vehicle or Premarin six months later, and all rats were trained in the Morris water maze. Premarin improved spatial learning and memory in nulliparous rats, but impaired early learning in primiparous rats. With training, primiparity increased hippocampal neurogenesis, and Premarin decreased immature neurons, regardless of parity. Moreover, Premarin increased serum tumor necrosis factor (TNF) α and the CXC chemokine ligand 1 (CXCL1) in nulliparous, but not primiparous, trained rats. However, Premarin decreased the expression of the immediate early gene zif268 in the dorsal CA3 region in primiparous rats after training. Thus, primiparity alters how Premarin affects spatial learning, neuronal activation, and serum cytokines. These findings have implications for the treatment of age-associated cognitive decline in women.
Subject
Parity; Aging; Memory; Estrone; Premarin; Neurogenesis; Hippocampus; Cytokines
Genre
Article; Postprint
Type
Text
Language
eng
Date Available
2019-06-30
Provider
Vancouver : University of British Columbia Library
Rights
Attribution-NonCommercial-NoDerivatives 4.0 International
DOI
10.14288/1.0369248
URI
http://hdl.handle.net/2429/66622
Affiliation
Arts, Faculty of; Medicine, Faculty of; Psychology, Department of
Citation
Galea, L. A., Roes, M. M., Dimech, C. J., Chow, C., Mahmoud, R., Lieblich, S. E., & Duarte-Guterman, P. (2018). Premarin has opposing effects on spatial learning, neural activation, and serum cytokine levels in middle-aged female rats depending on reproductive history. Neurobiology of Aging.
Publisher DOI
10.1016/j.neurobiolaging.2018.06.030
Peer Review Status
Reviewed
Scholarly Level
Faculty; Researcher; Postdoctoral; Graduate
Rights URI
http://creativecommons.org/licenses/by-nc-nd/4.0/
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Attribution-NonCommercial-NoDerivatives 4.0 International