Role of Estrogen Replacement Therapy in Memory Enhancement and the Prevention of Neuronal Loss Associated With Alzheimer’s Disease

Simpkins, James W.; Green, Pattie S.; Gridley, Kelly E.; Singh, Meharvan; Fiebre, NancyEllen C de; Rajakumar, G.

doi:10.1016/s0002-9343(97)00260-x

Cited by 243 publications

(131 citation statements)

References 30 publications

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“…As suggested by many investigators, estrogen and neurotrophins such as NGF and BDNF may be relevant to the etiology of Alzheimer's disease (AD; [119,120]). Clinical studies have shown that reduced BDNF may be an early marker of the disease, since both proBDNF and BDNF decline prior to the end stages of AD.…”

Section: Implications For Neurological and Psychiatric Disease A mentioning

confidence: 99%

Estrogen and brain-derived neurotrophic factor (BDNF) in hippocampus: Complexity of steroid hormone-growth factor interactions in the adult CNS

Scharfman

MacLusky

2006

Frontiers in Neuroendocrinology

270

202

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In the CNS, there are widespread and diverse interactions between growth factors and estrogen. Here we examine the interactions of estrogen and brain-derived neurotrophic factor (BDNF), two molecules that have historically been studied separately, despite the fact that they seem to share common targets, effects, and mechanisms of action. The demonstration of an estrogen-sensitive response element on the BDNF gene provided an impetus to explore a direct relationship between estrogen and BDNF, and predicted that the effects of estrogen, at least in part, might be due to the induction of BDNF. This hypothesis is discussed with respect to the hippocampus, where substantial evidence has accumulated in favor of it, but alternate hypotheses are also raised. It is suggested that some of the interactions between estrogen and BDNF, as well as the controversies and implications associated with their respective actions, may be best appreciated in light of the ability of BDNF to induce neuropeptide Y (NPY) synthesis in hippocampal neurons. Taken together, this tri-molecular cascade, estrogen-BDNF-NPY, may be important in understanding the hormonal regulation of hippocampal function. It may also be relevant to other regions of the CNS where estrogen is known to exert profound effects, such as amygdala and hypothalamus; and may provide greater insight into neurological disorders and psychiatric illness, including Alzheimer's disease, depression and epilepsy.

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Section: Implications For Neurological and Psychiatric Disease A mentioning

confidence: 99%

Estrogen and brain-derived neurotrophic factor (BDNF) in hippocampus: Complexity of steroid hormone-growth factor interactions in the adult CNS

Scharfman

MacLusky

2006

Frontiers in Neuroendocrinology

270

202

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“…This is significant in light of the influence estrogens have not only on reproductive function, but cognition and memory. This is especially true in postmenopausal women where a lack of estrogen increases the incidence of Alzheimer's disease [2,42,45,46,56,85,104,107,109,117].…”

Section: Malesmentioning

confidence: 99%

Neurobehavioral effects of dietary soy phytoestrogens

Lephart

West

Weber

et al. 2002

Neurotoxicology and Teratology

190

117

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“…For example, ovariectomy (ovx) decreases spatial memory, and ovxed female rats treated with E perform better than ovxed females treated with vehicle on a number of spatial memory tasks that utilize working memory including the Morris water maze, object place memory task, and the radial arm maze (Bimonte and Denenberg, 1999;Gibbs 1999;Luine et al, 1998;Luine et al, 2003;Packard, 1998;Sandstrom and Williams, 2001;Simpkins et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

Human chorionic gonadotropin (a luteinizing hormone homologue) decreases spatial memory and increases brain amyloid-β levels in female rats

Berry

Tomidokoro

Ghiso

et al. 2008

Hormones and Behavior

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Numerous studies have suggested that estradiol (E) improves spatial memory as female rats with E perform better than those without E. However there is an inverse relationship between E and luteinizing hormone (LH) levels and LH could play a role. We examined whether treatment with the LH homologue human chorionic gonadotropin (hCG), would impair spatial memory of adult Etreated female rats. In the Object Location Memory Task, ovariectomized (ovxed) rats treated with E and either a single high dose (400IU/kg) or a lower repeated dose of hCG (75 IU/kg hourly for 8 hours) showed spatial memory disruption compared to ovxed rats treated with estradiol alone. Impairment was attributed to memory disruption as performance improved with shortened delay between task exposure and testing. Tests on another spatial memory task, the Barnes maze, confirmed that hCG (400IU/kg) can impair memory: although E + veh treated animals made significantly fewer hole errors across time, E + hCG treated did not. In humans, high LH levels have been correlated with Alzheimer's Disease (AD). Because brain amyloid-beta (Aβ) species have been implicated as a toxic factor thought to cause memory loss in AD, we analyzed whether hCG-treated animals had increased Aβ levels. Levels of Aβ from whole brains or hippocampi were assessed by Western Blot. hCG treatment to E-implanted females significantly increased soluble Aβ40 and Aβ42 levels. These results indicate that high levels of LH/hCG can impair spatial memory, and an increase in brain Aβ species may account for the memory impairment in hCG-treated rats.

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Role of Estrogen Replacement Therapy in Memory Enhancement and the Prevention of Neuronal Loss Associated With Alzheimer’s Disease

Cited by 243 publications

References 30 publications

Estrogen and brain-derived neurotrophic factor (BDNF) in hippocampus: Complexity of steroid hormone-growth factor interactions in the adult CNS

Estrogen and brain-derived neurotrophic factor (BDNF) in hippocampus: Complexity of steroid hormone-growth factor interactions in the adult CNS

Neurobehavioral effects of dietary soy phytoestrogens

Human chorionic gonadotropin (a luteinizing hormone homologue) decreases spatial memory and increases brain amyloid-β levels in female rats

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