Sexual neurosteroids and synaptic plasticity in the hippocampus

Fester, Lars; Rune, Gabriele M.

doi:10.1016/j.brainres.2014.10.033

Cited by 73 publications

(49 citation statements)

References 58 publications

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“…Male and female neurons have steroidogenic activity and are able to synthesize the oestradiol precursor testosterone from cholesterol317. In addition, as shown here and in agreement with previous findings181920, both male and female neurons express aromatase, the enzyme that converts testosterone in oestradiol. To test whether endogenous oestradiol is involved in the enhanced expression and development of female neurons at 2DIV, we incubated the cultures with letrozole, an inhibitor of aromatase.…”

Section: Discussionsupporting

confidence: 92%

Oestradiol synthesized by female neurons generates sex differences in neuritogenesis

Ruiz-Palmero

Ortiz-Rodriguez

Melcangi

et al. 2016

Sci Rep

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Testosterone produced by the foetal testis is converted by male neurons to oestradiol, which masculinizes neuronal morphology. Female neurons are known to synthesize oestradiol in absence of exogenous testosterone. However, the role of neuronal oestradiol on the differentiation of foetal female neurons is unknown. Here we show that, due to endogenous neuronal oestradiol synthesis, female hippocampal neurons have higher expression of the neuritogenic protein Neurogenin 3 and enhanced neuritogenesis than males. Exogenous application of testosterone or its metabolite dihydrotestosterone increases Neurogenin 3 expression and promotes neuritogenesis in males, but reduces these parameters in females. Together our data indicate that gonadal-independent oestradiol synthesis by female neurons participates in the generation of sex differences in hippocampal neuronal development.

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Section: Discussionsupporting

confidence: 92%

Oestradiol synthesized by female neurons generates sex differences in neuritogenesis

Ruiz-Palmero

Ortiz-Rodriguez

Melcangi

et al. 2016

Sci Rep

Self Cite

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“…Pretreatment with ERβ blocker PHTTP markedly reduced but, in contrast to effects in males, did not eliminate response enhancement by estradiol (E2: 25.1±10.55%, E2+PHTPP: 13.37±8.52%; p=0.027; E2+PHTPP vs baseline, p=0.004; Fig 1g) whereas ERα and GPER1 antagonists had no effect (E2: 24 Many studies have shown that E2 increases numbers of spines (Hara et al, 2015;Luine and Frankfurt, 2012;Mukai et al, 2007) and spine synapses (Fester and Rune, 2015;Leranth et al, 2000) but whether this effect occurs quickly enough to contribute to the rapid facilitation of synaptic responses is unclear. Accordingly, we used FDT to count numbers of PSD95-immunopositive (+) synapses in CA1 SR of slices harvested 5-30 min after E2 perfusion onset: the steroid did not increase numbers of immunolabeled PSDs through 30 minutes (Fig 1i).…”

Section: Synaptic Localization Of Estrogen Receptor (Er) α and Erßmentioning

confidence: 91%

Estrogen’s Effects on Excitatory Synaptic Transmission Entail Integrin and TrkB Transactivation and Depend Upon β1-integrin function

Wang

Kantorovich

Babayan

et al. 2016

Neuropsychopharmacol

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Estradiol (E2) perfusion rapidly increases the strength of fast excitatory transmission and facilitates long-term potentiation in the hippocampus, two effects likely related to its memory-enhancing properties. Past studies showed that E2's facilitation of transmission involves activation of RhoA signaling leading to actin polymerization in dendritic spines. Here we report that brief exposure of adult male hippocampal slices to 1 nM E2 increases the percentage of postsynaptic densities associated with high levels of immunoreactivity for activated forms of the BDNF receptor TrkB and β1-integrins, two synaptic receptors that engage actin regulatory RhoA signaling. The effects of E2 on baseline synaptic responses were unaffected by pretreatment with the TrkB-Fc scavenger for extracellular BDNF or TrkB antagonism, but were eliminated by neutralizing antisera for β1-integrins. E2 effects on synaptic responses were also absent in conditional β1-integrin knockouts, and with inhibition of matrix metalloproteinases, extracellular enzymes that generate integrin ligands. We propose that E2, acting through estrogen receptor-β, transactivates synaptic TrkB and β1-integrin, and via mechanisms dependent on integrin activation and signaling, reversibly reorganizes the spine cytoskeleton and thereby enhances synaptic responses in adult hippocampus.

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“…Furthermore, locally produced E 2 plays a crucial role in estrogen-mediated facilitation of LTP in this region (Grassi et al, 2011;Fester and Rune, 2015). Although the mechanisms by which E 2 regulates synaptic plasticity in CA1 have been extensively studied, less attention has been paid to its effects in other hippocampal areas, such as CA3 or dentate gyrus (DG).…”

Section: Introductionmentioning

confidence: 99%

A novel form of synaptic plasticity in field CA3 of hippocampus requires GPER1 activation and BDNF release

Briz¹,

Liu²,

Zhu³

et al. 2015

J Exp Med

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Sexual neurosteroids and synaptic plasticity in the hippocampus

Cited by 73 publications

References 58 publications

Oestradiol synthesized by female neurons generates sex differences in neuritogenesis

Oestradiol synthesized by female neurons generates sex differences in neuritogenesis

Estrogen’s Effects on Excitatory Synaptic Transmission Entail Integrin and TrkB Transactivation and Depend Upon β1-integrin function

A novel form of synaptic plasticity in field CA3 of hippocampus requires GPER1 activation and BDNF release

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