期刊
BRAIN RESEARCH
卷 1379, 期 -, 页码 176-187出版社
ELSEVIER
DOI: 10.1016/j.brainres.2010.12.064
关键词
Estrogen; Hormone replacement therapy; Perimenopause
资金
- NHLBI NIH HHS [HL098351, R01 HL098351, P01 HL018974, R01 HL098351-01A1, HL096571, HL18974, P01 HL018974-30, P01 HL096571-03, P01 HL096571] Funding Source: Medline
- NIA NIH HHS [P01 AG016765-10, P01 AG016765, AG016765] Funding Source: Medline
- NIDA NIH HHS [R01 DA008259, DA08259, R01 DA008259-17] Funding Source: Medline
- NIDDK NIH HHS [DK07313, T32 DK007313] Funding Source: Medline
Current rodent models of menopause fail to adequately recapitulate the menopause transition. The intact aging model fails to achieve very low estrogen levels, and the ovariectomy model lacks a perimenopause phase. A new rodent model of accelerated ovarian failure (AOF) successfully replicates human perimenopause and postrnenopause, including estrous acyclicity and fluctuating, followed by undetectable, estrogen levels, and allows for the dissociation of the effects of hormone levels from the effects of aging. In this model, an ovotoxic chemical, 4-vinylcyclohexene diepoxide (VCD), selective for primary and primordial follicles, is injected intraperitonelly in animals for 15 days. As the mature follicle population is depleted through natural cycling, ovarian failure follows increasing periods of acyclity. Administered at low doses, VCD specifically causes apoptotic cell death of primordial follicles but does not affect other peripheral tissues, including the liver and spleen, nor does it affect brain inflammation markers. In addition to reducing confounds associated with genetic and surgical manipulations, the AOF model maintains the presence of ovarian tissue which importantly parallels to the menopause transition in humans. The VCD injection procedure can be applied to studies using transgenic or knockout mice strains, or in other disease-state models (e.g., ischemia, atherosclerosis, or diabetes). This AOF model of menopause will generate new insights into women's health particularly in determining the critical periods (i.e., a window of opportunity) during perimenopause for restoring ovarian hormones for the most efficacious effect on memory and mood disorders as well as other menopausal symptoms. (C) 2011 Elsevier B.V. All rights reserved.
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