Rapid and local neuroestrogen synthesis supports long-term potentiation of hippocampal Schaffer collaterals-cornu ammonis 1 synapse in ovariectomized mice.
aromatase
electrophysiology
estrogen
hippocampus
synaptic plasticity
Journal
Journal of neuroendocrinology
ISSN: 1365-2826
Titre abrégé: J Neuroendocrinol
Pays: United States
ID NLM: 8913461
Informations de publication
Date de publication:
01 Oct 2024
01 Oct 2024
Historique:
revised:
31
07
2024
received:
19
02
2024
accepted:
04
09
2024
medline:
1
10
2024
pubmed:
1
10
2024
entrez:
1
10
2024
Statut:
aheadofprint
Résumé
In aging women, cognitive decline and increased risk of dementia have been associated with the cessation of ovarian hormones production at menopause. In the brain, presence of the key enzyme aromatase required for the synthesis of 17-β-estradiol (E2) allows for local production of E2 in absence of functional ovaries. Understanding how aromatase activity is regulated could help alleviate the cognitive symptoms. In female rodents, genetic or pharmacological reduction of aromatase activity over extended periods of time impair memory formation, decreases spine density, and hinders long-term potentiation (LTP) in the hippocampus. Conversely, increased excitatory neurotransmission resulting in rapid N-methyl-d-aspartic acid (NMDA) receptor activation rapidly promotes neuroestrogen synthesis. This rapid modulation of aromatase activity led us to address the hypothesis that acute neuroestrogens synthesis is necessary for LTP at the Schaffer collateral-cornu ammonis 1 (CA1) synapse in absence of circulating ovarian estrogens. To test this hypothesis, we did electrophysiological recordings of field excitatory postsynaptic potential (fEPSPs) in hippocampal slices obtained from ovariectomized mice. To assess the impact of neuroestrogens synthesis on LTP, we applied the specific aromatase inhibitor, letrozole, before the induction of LTP with a theta burst stimulation protocol. We found that blocking aromatase activity prevented LTP. Interestingly, exogenous E2 application, while blocking aromatase activity, was not sufficient to recover LTP in our model. Our results indicate the critical importance of rapid, activity-dependent local neuroestrogens synthesis, independent of circulating hormones for hippocampal synaptic plasticity in female rodents.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e13450Subventions
Organisme : NIA NIH HHS
ID : RF1AG041374
Pays : United States
Informations de copyright
© 2024 The Author(s). Journal of Neuroendocrinology published by John Wiley & Sons Ltd on behalf of British Society for Neuroendocrinology.
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