Beta estrogen receptor knockout (BERKO) mice present attenuated hippocampal CA1 long-term potentiation and related memory deficits in contextual fear conditioning

Day, Mark L.; Sung, Amy; Logue, Sheree F.; Bowlby, Mark R.; Arias, Robert

doi:10.1016/j.bbr.2005.05.011

Cited by 65 publications

(44 citation statements)

References 22 publications

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“…ERRα and ERRβ both show increased expression after fear conditioning. Because ERRs bind to many of the same targets as the ER and estrogen signaling contributes to memory formation (6,9), the relationship between this increase in ERR expression and estrogen signaling may be an interesting area of future study. Alternatively, the role played by ERRs in mitochondrial function and energy metabolism (33) may suggest that these processes contribute to learning and memory as has been suggested elsewhere (34).…”

Section: Discussionmentioning

confidence: 99%

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NR4A nuclear receptors support memory enhancement by histone deacetylase inhibitors

Hawk¹,

Bookout²,

Poplawski³

et al. 2012

J. Clin. Invest.

134

176

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The formation of a long-lasting memory requires a transcription-dependent consolidation period that converts a short-term memory into a long-term memory. Nuclear receptors compose a class of transcription factors that regulate diverse biological processes, and several nuclear receptors have been implicated in memory formation. Here, we examined the potential contribution of nuclear receptors to memory consolidation by measuring the expression of all 49 murine nuclear receptors after learning. We identified 13 nuclear receptors with increased expression after learning, including all 3 members of the Nr4a subfamily. These CREB-regulated Nr4a genes encode ligand-independent "orphan" nuclear receptors. We found that blocking NR4A activity in memory-supporting brain regions impaired long-term memory but did not impact short-term memory in mice. Further, expression of Nr4a genes increased following the memory-enhancing effects of histone deacetylase (HDAC) inhibitors. Blocking NR4A signaling interfered with the ability of HDAC inhibitors to enhance memory. These results demonstrate that the Nr4a gene family contributes to memory formation and is a promising target for improving cognitive function.

show abstract

Section: Discussionmentioning

confidence: 99%

“…For instance, agonists for glucocorticoid receptors, estrogen receptors (ERs), PPARs, and retinoic acid receptors (RARs) can improve long-term memory formation under certain conditions (5)(6)(7)(8). Additionally, mice with mutations in the Erb (9), Rarb (10), or the orphan NR Nr4a2 have deficits in long-term memory (11).…”

Section: Introductionmentioning

confidence: 99%

NR4A nuclear receptors support memory enhancement by histone deacetylase inhibitors

Hawk¹,

Bookout²,

Poplawski³

et al. 2012

J. Clin. Invest.

134

176

View full text Add to dashboard Cite

show abstract

“…al. [298] recently demonstrated that hippocampal slices from ER-β knockout mice have significant attenuations of LTP, and that ER-β knockout mice display significant impairment in hippocampal-mediated fear conditioning. Unfortunately, none of these studies examined spine density or other measures of synaptic plasticity in the ER knockout mice.…”

Section: Mechanisms Of Estrogen Regulation Of Synaptic Plasticitymentioning

confidence: 99%

Neurotrophic and neuroprotective actions of estrogen: Basic mechanisms and clinical implications

et al. 2007

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Estrogen is an important hormone signal that regulates multiple tissues and functions in the body. This review focuses on the neurotrophic and neuroprotective actions of estrogen in the brain, with particular emphasis on estrogen actions in the hippocampus, cerebral cortex and striatum. Sex differences in the risk, onset and severity of neurodegenerative disease such as Alzheimer's disease, Parkinson's disease and stroke are well known, and the potential role of estrogen as a neuroprotective factor is discussed in this context. The review assimilates a complex literature that spans research in humans, non-human primates and rodent animal models and attempts to contrast and compare the findings across species where possible. Current controversies regarding the WHI (Women's Health Initiative) study, its ramifications, concerns and the new studies needed to address these concerns are also addressed. Signaling mechanisms underlying estrogen-induced neuroprotection and synaptic plasticity are reviewed, including the important concepts of genomic versus nongenomic mechanisms, types of estrogen receptor involved and their subcellular targeting, and implicated downstream signaling pathways and mediators. Finally, a multicellular mode of estrogen action in the regulation of neuronal survival and neurotrophism is discussed, as are potential future directions for the field.

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“…For example, ERα mediates the neuroprotective effects of E2 against ischemic brain injury (Dubal, 2001) whereas ERβ is responsible for the anti-anxiety and anti-depressive effects of E2 (Walf, 2007). However, it has been reported that ERβ is involved in CA1 LTP and hippocampaldependent contextual fear conditioning (Day, 2005), so a closer examination of ERβ-selective agonists in the hippocampus is needed to fully appreciate the role of ERβ in the activation of αCaMKII within this brain region.…”

Section: Discussionmentioning

confidence: 99%

Modulation of αCaMKII signaling by rapid ERα action

et al. 2008

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The estrogen receptor (ER) subtypes, ERα and ERβ, modulate numerous signaling cascades in the brain to result in a variety of cell fates including neuronal differentiation. We report here that 17β-estradiol (E2) rapidly stimulates the autophosphorylation of α-Ca 2+ /calmodulin-dependent kinase II (αCaMKII) in immortalized NLT GnRH neurons, primary hippocampal neurons, and Cos7 cells cotransfected with ERα and αCaMKII. The E2-induced αCaMKII autophosphorylation is ERα-and Ca 2+ /calmodulin (CaM)-dependent. Interestingly, the hormone-dependent association of ERα with αCaMKII attenuates the positive effect of E2 on αCaMKII autophosphorylation, suggesting that ERα plays a complex role in modulating αCaMKII activity and may function to fine-tune αCaMKII-triggered signaling events. However, it appears as though the activating signal of E2 dominates the negative effect of ER since there is a clear, positive downstream response to E2-activated αCaMKII; pharmacological inhibitors and RNAi technology show that targets of ERα-mediated αCaMKII signaling include extracellular signal-regulated kinase 1/2 (ERK1/2), cAMP response elementbinding protein (CREB), and microtubule associated protein 2 (MAP2). These findings suggest a novel model for the modulation of αCaMKII signaling by ERα, which provides a molecular link as to how E2 might influence brain function.

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Beta estrogen receptor knockout (BERKO) mice present attenuated hippocampal CA1 long-term potentiation and related memory deficits in contextual fear conditioning

Cited by 65 publications

References 22 publications

NR4A nuclear receptors support memory enhancement by histone deacetylase inhibitors

NR4A nuclear receptors support memory enhancement by histone deacetylase inhibitors

Neurotrophic and neuroprotective actions of estrogen: Basic mechanisms and clinical implications

Modulation of αCaMKII signaling by rapid ERα action

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