Neural 17β-estradiol facilitates long-term potentiation in the hippocampal CA1 region

Grassi, Silvia; Tozzi, Alessandro; Costa, Cinzia; Tantucci, Michela; Colcelli, Elisa; Scarduzio, Mariangela; Calabresi, Paolo; Pettorossi, Vito Enrico

doi:10.1016/j.neuroscience.2011.06.078

Cited by 52 publications

(57 citation statements)

References 31 publications

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“…We should mention that preliminary studies using a different approach, icv administration of an aromatase inhibitor, letrozole, confirmed a neuroprotective and anti-inflammatory role of brain-derived E2 in the hippocampus ( unpublished observations ). In addition to the neuroprotective and anti-inflammatory role for local E2 revealed in our study, work by other investigators has provided evidence that brain-derived E2 can also regulate synaptic plasticity [19, 21, 26–28], LTP [29, 30], and protect the hippocampus from excitotoxic damage [33]. …”

Section: Discussionsupporting

confidence: 57%

“…With respect to the hippocampus, treatment of cultured mouse hippocampal neurons with an aromatase inhibitor has been reported to result in a significant decrease in axon outgrowth and dendritic spines in the CA1 region [19, 21, 26–28], as well as a significant decrease of long-term potentiation (LTP) amplitude, dendritic spines and synapses in hippocampal slices in vitro [29, 30]. These results suggest that local E2 in the hippocampus may modulate synaptic function.…”

Section: Introductionmentioning

confidence: 99%

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Brain-derived estrogen exerts anti-inflammatory and neuroprotective actions in the rat hippocampus

Zhang

Wang

Tang

et al. 2014

Molecular and Cellular Endocrinology

107

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17β-estradiol (E2) has been implicated to play a critical role in neuroprotection, synaptic plasticity, and cognitive function. Classically, the role of gonadal-derived E2 in these events is well established, but the role of brain-derived E2 is less clear. To address this issue, we investigated the expression, localization, and modulation of aromatase and local E2 levels in the hippocampus following global cerebral ischemia (GCI) in adult ovariectomized rats. Immunohistochemistry (IHC) revealed that the hippocampal regions CA1, CA3 and dentate gyrus (DG) exhibited high levels of immunoreactive aromatase staining, with aromatase being co-localized primarily in neurons in non-ischemic animals. Following GCI, aromatase became highly expressed in GFAP-positive astrocytes in the hippocampal CA1 region at 2–3 days post GCI reperfusion. An ELISA for E2 and IHC for E2 confirmed the GCI-induced elevation of local E2 in the CA1 region and that the increase in local E2 occurred in astrocytes. Furthermore, central administration of aromatase antisense (AS) oligonucleotides, but not missense (MS) oligonucleotides, blocked the increase in aromatase and local E2 in astrocytes after GCI, and resulted in a significant increase in GCI-induced hippocampal CA1 region neuronal cell death and neuroinflammation. As a whole, these results suggest that brain-derived E2 exerts important neuroprotective and anti-inflammatory actions in the hippocampal CA1 region following GCI.

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Section: Discussionsupporting

confidence: 57%

Section: Introductionmentioning

confidence: 99%

Brain-derived estrogen exerts anti-inflammatory and neuroprotective actions in the rat hippocampus

Zhang

Wang

Tang

et al. 2014

Molecular and Cellular Endocrinology

107

View full text Add to dashboard Cite

show abstract

“…Regarding metabolites of testosterone that act on estrogen receptors [(17β-estradiol and 5α-androstane- 3β , 17β-diol (Pak et al, 2004; Handa et al, 2008; Handa et al 2011)], one cannot rule out effects of these metabolites either. Although some studies suggest that males are relatively insensitive to 17β-estradiol compared to females, for example in the number of hippocampal CA1 spine synapses that increase in response to 17β-estradiol administration (Maclusky et al, 2006; Woolley and McEwen, 1992; Cooke and Woolley, 2005; Woolley, 2007), and other measures of hippocampal function (Huang and Woolley, 2012; Vierk et al, 2012), other studies have shown robust effects of 17β-estradiol in males (Foy et al, 1999; Mukai et al, 2006; Murakami et al, 2006; Kramar et al, 2009; Mukai et al, 2009; Grassi et al, 2011; Kramar et al, 2012). …”

Section: Discussionmentioning

confidence: 99%

Testosterone Depletion in Adult Male Rats Increases Mossy Fiber Transmission, LTP, and Sprouting in Area CA3 of Hippocampus

et al. 2013

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Androgens have dramatic effects on neuronal structure and function in hippocampus. However, androgen depletion does not always lead to hippocampal impairment. To address this apparent paradox, we evaluated the hippocampus of adult male rats after gonadectomy (Gdx) or sham surgery. Surprisingly, Gdx rats showed increased synaptic transmission and long-term potentiation (LTP) of the mossy fiber (MF) pathway. Gdx rats also exhibited increased excitability and MF sprouting. We then addressed the possible underlying mechanisms, and found that Gdx induced a long-lasting upregulation of MF brain-derived neurotrophic factor (BDNF) immunoreactivity. Antagonism of Trk receptors, which bind neurotrophins such as BDNF, reversed the increase in MF transmission, excitability and LTP in Gdx rats, but there were no effects of Trk antagonism in sham controls. To determine which androgens were responsible, the effects of testosterone metabolites dihydrotestosterone (DHT) and 5α-androstane-3α,17β-diol were examined. Exposure of slices to 50 nM DHT decreased the effects of Gdx on MF transmission but 50 nM 5α-androstane-3α,17β-diol had no effect. Remarkably, there was no effect of DHT in control males. The data suggest that a Trk- and androgen receptor-sensitive form of MF transmission and synaptic plasticity emerges after Gdx. We suggest that androgens may normally be important in area CA3 to prevent hyperexcitability and aberrant axon outgrowth, but limit MF synaptic transmission and some forms of plasticity. The results also suggest a potential explanation for the maintenance of hippocampal-dependent cognitive function after androgen depletion: a reduction in androgens may lead to compensatory upregulation of MF transmission and plasticity.

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“…Work using an aromatase inhibitor has provided evidence that endogenous E2 is required for LTP (Grassi et al, 2011) but didn't establish if this reflects constitutive actions vs. release during theta bursts. Thus, it remains to be seen whether brain-derived estrogen serves a constitutive role to maintain normal synaptic transmission and/or whether it is released only following activity-dependent activation.…”

Section: Summary and Discussionmentioning

confidence: 99%

Estrogen promotes learning-related plasticity by modifying the synaptic cytoskeleton

et al. 2013

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Estrogen's acute, facilitatory effects on glutamatergic transmission and long-term potentiation (LTP) provide a potential explanation for the steroid's considerable influence on behavior. Recent work has identified mechanisms underlying these synaptic actions. Brief infusion of 17β-estradiol (E2) into adult male rat hippocampal slices triggers actin polymerization within dendritic spines via a signaling cascade beginning with the GTPase RhoA and ending with inactivation of the filament severing protein cofilin. Blocking this sequence, or actin polymerization itself, eliminates E2's effects on synaptic physiology. Notably, the theta burst stimulation used to induce LTP activates the same signaling pathway as E2 plus events that stabilize the reorganization of the sub-synaptic cytoskeleton. These observations suggest that E2 elicits a partial form of LTP, resulting in an increase of fast EPSP's and a reduction in the threshold for lasting synaptic changes. While E2's effects on the cytoskeleton could be direct, results described here indicate that the hormone activates synaptic TrkB receptors for Brain Derived Neurotrophic Factor, a releasable neurotrophin that stimulates the RhoA to cofilin pathway. It is therefore possible that E2 acts via transactivation of neighboring receptors to modify the composition and structure of excitatory contacts. Finally, there is the question of whether a loss of acute synaptic actions contributes to the memory problems associated with estrogen depletion. Initial tests found that ovariectomy in middle-aged rats disrupts RhoA signaling, actin polymerization, and LTP consolidation. Acute applications of E2 reversed these defects, a result consistent with the idea that disturbances to actin management are one cause of behavioral effects that emerge with reductions in steroid levels.

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Neural 17β-estradiol facilitates long-term potentiation in the hippocampal CA1 region

Cited by 52 publications

References 31 publications

Brain-derived estrogen exerts anti-inflammatory and neuroprotective actions in the rat hippocampus

Brain-derived estrogen exerts anti-inflammatory and neuroprotective actions in the rat hippocampus

Testosterone Depletion in Adult Male Rats Increases Mossy Fiber Transmission, LTP, and Sprouting in Area CA3 of Hippocampus

Estrogen promotes learning-related plasticity by modifying the synaptic cytoskeleton

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