Estradiol initially enhances but subsequently suppresses (via adrenal steroids) granule cell proliferation in the dentate gyrus of adult female rats

Ormerod, Brandi K.; Lee, T. T-Y.; Galea, Liisa A.M.

doi:10.1002/neu.10181

Cited by 168 publications

(146 citation statements)

References 89 publications

Supporting

Mentioning

135

Contrasting

Order By: Relevance

“…These doses were chosen based on earlier studies investigating spatial learning and hippocampal neurogenesis (Tanapat et al, 1999;Ormerod et al, 2003;Holmes et al, 2002;Tanapat et al, 2005;Barha et al, 2009). A high dose of 10 mg 17b-estradiol was chosen because it results in circulating levels of estradiol observed on the morning of proestrus (Viau and Meaney, 1991) and has been shown to enhance cell proliferation 30 min (Barha et al, 2009), 2 h (Tanapat et al, 1999;Tanapat et al, 2005), and 4 h (Ormerod et al, 2003;Barha et al, 2009) after injection. However, this same dose produces supraphysiological levels of estradiol shortly after administration (Woolley and McEwen, 1993).…”

Section: Drug Treatmentmentioning

confidence: 99%

Low Doses of 17α-Estradiol and 17β-Estradiol Facilitate, Whereas Higher Doses of Estrone and 17α- and 17β-Estradiol Impair, Contextual Fear Conditioning in Adult Female Rats

Barha

Dalton

Galea

2009

Neuropsychopharmacol

109

View full text Add to dashboard Cite

Estrogens are known to exert significant structural and functional effects in the hippocampus of adult rodents. In particular, 17b-estradiol can improve, impair, or have no effect on hippocampus-dependent learning and memory depending on dose and time of administration. The effects of other forms of estrogen, such as estrone and 17a-estradiol, on hippocampus-dependent learning have not been as thoroughly investigated. Therefore, the purpose of this study was to investigate the effects of 17b-estradiol, estrone, and 17a-estradiol at three different doses on two different tasks: hippocampus-dependent contextual fear conditioning and hippocampusindependent cued fear conditioning. Adult ovariectomized female rats were injected with one of the estrogens at one of the three doses 30 mins before conditioning to assess the rapid effects of these estrogens on acquisition. Twenty-four hours later memory for the context was examined and 1 h later memory for the cue (tone) was assessed. Levels of synaptophysin were examined in the dorsal hippocampus of rats to identify a potential synaptic correlate of hormonal effects on contextual fear conditioning. Low 17b-estradiol and 17a-estradiol enhanced, whereas high 17b-estradiol and 17a-estradiol impaired, contextual fear conditioning. Only the middle dose of estrone severely impaired contextual fear conditioning. Estrogens did not alter performance in the hippocampus-independent cued task. Synaptophysin expression was increased by estrone (at a middle and high dose) and 17b-estradiol (at a middle dose) in the CA3 region of the hippocampus and was not correlated with cognition. The results of this study indicate that estradiol can positively or negatively influence hippocampus-dependent learning and memory, whereas estrone impairs hippocampus-dependent learning and memory in a dose-dependent manner. These results have important therapeutic implications, as estrone, a main component of a widely used hormone replacement therapy, was shown to have either a negative effect or no effect on learning and memory. It may be possible to use 17a-estradiol and lower doses of estrogens as potential alternatives in hormone replacement therapies.

show abstract

Section: Drug Treatmentmentioning

confidence: 99%

Low Doses of 17α-Estradiol and 17β-Estradiol Facilitate, Whereas Higher Doses of Estrone and 17α- and 17β-Estradiol Impair, Contextual Fear Conditioning in Adult Female Rats

Barha

Dalton

Galea

2009

Neuropsychopharmacol

109

View full text Add to dashboard Cite

show abstract

“…Indeed, the similarities do not stop with those listed above. The rate of dentate gyrus neurogenesis is increased by both estrogen and BDNF [72][73][74][75]. The influence of both estrogen and BDNF also applies to glia [76][77][78], although this is not as well documented as their effects on neurons.…”

Section: Comparison Of Estrogen and Bdnf Actions In Hippocampus-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

View full text Add to dashboard Cite

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.

show abstract

“…Estradiol rapidly enhances hippocampus-dependent memory (Daniel 2006;Luine 2008;Luine and Frankfurt 2012), most likely through estradiol's effects on neurogenesis (Ormerod et al 2003;Mazzucco et al 2006;Li et al 2011), and synaptic and structural plasticity, including enhanced dendritic spine density in area CA1 pyramidal cells (Woolley and McEwen 1992;Rudick and Woolley 2001). It is also an important factor that is known to affect learning strategy in female rodents, enhancing the hippocampus-sensitive place strategy over striatumdependent response strategy (Korol and Kolo 2002;Daniel and Lee 2004;Korol et al 2004;Davis et al 2005;Tunur et al 2010).…”

Section: Downstream Regulatory Element Antagonist Modulator (Dream)/ mentioning

confidence: 99%

DREAM/calsenilin/KChIP3 modulates strategy selection and estradiol-dependent learning and memory

2013

View full text Add to dashboard Cite

Downstream regulatory element antagonist modulator (DREAM)/calsenilin(C)/K+ channel interacting protein 3 (KChIP3) is a multifunctional Ca 2+ -binding protein highly expressed in the hippocampus that inhibits hippocampus-sensitive memory and synaptic plasticity in male mice. Initial studies in our lab suggested opposing effects of DR/C/K3 expression in female mice. Fluctuating hormones that occur during the estrous cycle may affect these results. In this study, we hypothesized that DR/C/K3 interacts with 17b-estradiol, the primary estrogen produced by the ovaries, to play a role in hippocampus function. We investigated the role of estradiol and DR/C/K3 in learning strategy in ovariectomized (OVX) female mice. OVX WT and DR/C/K3 knockout (KO) mice were given three injections of vehicle (sesame oil) or 17b-estradiol benzoate (0.25 mg in 100 mL sesame oil) 48, 24, and 2 h before training and testing. DR/C/K3 and estradiol had a time-dependent effect on strategy use in the female mice. Male KO mice exhibited enhanced place strategy relative to WT 24 h after pre-exposure. Fear memory formation was significantly reduced in intact female KO mice relative to intact WT mice, and OVX reduced fear memory formation in the WT, but had no effect in the KO mice. Long-term potentiation in hippocampus slices from female mice was enhanced by circulating ovarian hormones in both WT and DR/C/K3 KO mice. Paired-pulse depression was not affected by ovarian hormones but was reduced in DR/C/K3 KO mice. These results provide the first evidence that DR/C/K3 plays a timing-dependent role in estradiol regulation of learning, memory, and plasticity.

show abstract

Estradiol initially enhances but subsequently suppresses (via adrenal steroids) granule cell proliferation in the dentate gyrus of adult female rats

Cited by 168 publications

References 89 publications

Low Doses of 17α-Estradiol and 17β-Estradiol Facilitate, Whereas Higher Doses of Estrone and 17α- and 17β-Estradiol Impair, Contextual Fear Conditioning in Adult Female Rats

Low Doses of 17α-Estradiol and 17β-Estradiol Facilitate, Whereas Higher Doses of Estrone and 17α- and 17β-Estradiol Impair, Contextual Fear Conditioning in Adult Female Rats

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

DREAM/calsenilin/KChIP3 modulates strategy selection and estradiol-dependent learning and memory

Contact Info

Product

Resources

About