Reducing luteinizing hormone levels after ovariectomy improves spatial memory: Possible role of brain-derived neurotrophic factor

Alzheimer's disease and other forms of cognitive decline are significantly more prevalent in post-menopausal women. Decreased estrogen levels, due to menopause or ovariectomy, may contribute to memory impairments and neurodegeneration. Another result of decreased estrogen levels is elevated lut...

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Bibliographic Details
Published in:Hormones and behavior 2020-02, Vol.118, p.104590-104590, Article 104590
Main Authors: Bohm-Levine, Nathaniel, Goldberg, Alexander R., Mariani, Monica, Frankfurt, Maya, Thornton, Janice
Format: Article
Language:English
Subjects:
Alzheimer's disease
Brain-derived neurotrophic factor
Estrogen
Luteinizing hormone
Spatial memory
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Summary:Alzheimer's disease and other forms of cognitive decline are significantly more prevalent in post-menopausal women. Decreased estrogen levels, due to menopause or ovariectomy, may contribute to memory impairments and neurodegeneration. Another result of decreased estrogen levels is elevated luteinizing hormone (LH). Elevated LH after menopause/ovariectomy has been shown to impair cognition in both human and animal studies. Lowering LH levels rescues spatial memory in ovariectomized (ovx) rodents, yet the mechanisms of these effects are still unclear. Estrogens appear to exert some of their effects on memory by increasing levels of brain-derived neurotrophic factor (BDNF) in the hippocampus. In these studies, we explored whether lowering LH may act by increasing BDNF. Ovx rats were treated with Antide, a gonadotropin releasing hormone receptor antagonist that lowers LH levels, or with estradiol. Both Antide and estradiol treatment enhanced spatial memory in ovx females. Both were found to be ineffective when a BDNF receptor antagonist was administered. Immunohistochemical analysis revealed that both Antide and estradiol increased BDNF expression in the hippocampus. Dendritic spine density on pyramidal cells in CA1 was unchanged by any treatment. These results provide evidence for a relationship between LH and BDNF in the hippocampus and demonstrate that estrogen-increasing and LH-lowering treatments may both require BDNF signaling in order to improve spatial memory. •Estradiol improved spatial memory in ovx rats and ANA-12, a brain-derived neurotrophic factor (BDNF) receptor antagonist, blocked this improvement•Lowering Luteinizing Hormone using Antide enhanced spatial memory in ovariectomized rats and ANA-12 blocked this spatial memory improvement•Both Antide and estradiol increased levels of immunoreactive BDNF in the hippocampus.•Neither Antide nor estradiol increased spine density in the hippocampal CA1 region
ISSN:0018-506X
1095-6867
DOI:10.1016/j.yhbeh.2019.104590