Estradiol Enhances Learning and Memory in a Spatial Memory Task and Effects Levels of Monoaminergic Neurotransmitters

Luine, Victoria N.; Richards, Shannon T.; Wu, Vincent; Beck, Kevin D.

doi:10.1006/hbeh.1998.1473

Cited by 407 publications

(289 citation statements)

References 45 publications

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“…For instance, many reports have indicated a relationship between estrogen and cognitive function in humans and rodents (Warren and Juraska, 1997;Luine et al, 1998;Markowska, 1999;Fugger et al, 2000;Heikkinen et al, 2002;Iivonen et al, 2006). In postmenopausal women and aged rodents, estrogen treatment enhances cognitive function (Drake et al, 2000;Keenan et al, 2001;Sherwin, 2002;Markowska and Savonenko, 2002;Frick et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

Age-related changes in the expression of ER-β mRNA in the female rat brain

Yamaguchi

Yuri

2007

Brain Research

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Estrogen is important for numerous physiological actions, most of which are mediated via the nuclear estrogen receptors (ERs), ER-α and ER-β, which modulate the transcription of target genes following estrogen binding. Estrogen functions change with age. In the present study, to reveal the effects of normal aging on ER-β expression in the brain, we examined ER-β expression at the transcriptional level using young (10 weeks), middle-aged (12 months) and old (24 months) intact female rats. In situ hybridization using a digoxigenin-labeled RNA probe was used to assess the number of ER-β mRNA-positive cells in each region in whole brain. ER-β mRNA-positive cells were detected throughout the brain in young female rats and were reduced in number in the olfactory bulb, cerebral cortex, hippocampus, accumbens nucleus, part of the amygdala and raphe nucleus of middle-aged rats, but did not decline further in number in aged animals. By contrast, the number of ER-β mRNA-positive cells was decreased in the hippocampus, caudate putamen, claustrum, accumbens nucleus, substantia nigra and cerebellum was not significantly different between young and middle-aged rats, but was decreased in old rats. These results indicate that the expression of ER-β mRNA in the female rat brain is differentially modulated during aging and that the changes are region specific.Section: 2) Nervous System Development, Regeneration and Aging

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Section: Discussionmentioning

confidence: 99%

Age-related changes in the expression of ER-β mRNA in the female rat brain

Yamaguchi

Yuri

2007

Brain Research

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“…Finally, for both estrogen and BDNF, the effects that have been observed exhibit unique and characteristic response patterns, that are not shared by any other humoral agent. Thus, estrogen has striking effects that range from alterations in behavior [5][6][7][8][9][10][11][12][13], structure (spine morphology, density, and spine synapses; Table 2), and physiology (potentiation of glutamatergic inputs in area CA1; Table 2) including specific receptormediated actions, such as actions at the NMDA receptor (although not exclusively; [14]). BDNF is the one other molecule that has been shown to exert many, if not all, of these same specific effects (Table 2).…”

Section: Estrogen and Bdnf In Hippocampus A Rationalementioning

confidence: 99%

“…This has been shown for male rats after manipulations that increase estradiol, and the reverse, that learning is worse when estradiol levels are low, for example in aromatase-knockout mice [42]. This has also been studied in female rats after ovariectomy and estradiol replacement, although it is difficult to compare some of these studies because doses of estradiol vary, as well as other potential factors such as age, time after ovariectomy, and housing [5][6][7][8][9][11][12][13]43]. The variability occurs not only in whether behavior is enhanced, but also the type of task.…”

Section: Comparison Of Estrogen and Bdnf Actions In Hippocampus-mentioning

confidence: 99%

“…The variability occurs not only in whether behavior is enhanced, but also the type of task. Thus, many studies of spatial learning (a classic hippocampal-dependent behavior) show an improvement after estradiol administration, but other types of memory can sometimes also improve, suggesting not only hippocampal effects but also non-hippocampal effects [5][6][7][8][9][11][12][13]43]. Learning appears to be enhanced on the morning of proestrus relative to other cycle stages or relative to ovariectomy [44].…”

Section: Comparison Of Estrogen and Bdnf Actions In Hippocampus-mentioning

confidence: 99%

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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

257

195

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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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“…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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Estradiol Enhances Learning and Memory in a Spatial Memory Task and Effects Levels of Monoaminergic Neurotransmitters

Cited by 407 publications

References 45 publications

Age-related changes in the expression of ER-β mRNA in the female rat brain

Age-related changes in the expression of ER-β mRNA in the female rat brain

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

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

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