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Neuron-Derived Estrogen-A Key Neuromodulator in Synaptic Function and Memory.

Darrell W Brann1, Yujiao Lu2, Jing Wang1

  • 1Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA.

International Journal of Molecular Sciences
|December 24, 2021
PubMed
Summary
This summary is machine-generated.

Neuron-derived 17β-estradiol (NDE2) acts as a neuromodulator, regulating synaptic plasticity and memory formation in the brain. This neurosteroid influences synapse density, synaptic transmission, and various forms of memory.

Keywords:
aromatasecognitionestradiolmemoryneuroestrogenneuromodulatorneurosteroidsteroid hormonesynapse

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Area of Science:

  • Neuroscience
  • Endocrinology
  • Molecular Biology

Background:

  • 17β-estradiol (E2) functions as both a steroid hormone and a neurosteroid.
  • Neuron-derived E2 (NDE2) is synthesized within neurons by aromatase, an enzyme localized at synapses.
  • NDE2 plays a critical role in modulating brain function.

Purpose of the Study:

  • To review evidence for the neuromodulatory role of NDE2 in synaptic plasticity and memory.
  • To elucidate the mechanisms by which NDE2 influences neuronal function and cognitive processes.

Main Methods:

  • Studies utilizing aromatase inhibitors and overexpression models.
  • Analysis of global and conditional forebrain neuron-specific aromatase knockout mice.
  • Investigation of estrogen receptor-mediated signaling pathways.

Main Results:

  • NDE2 is crucial for regulating synapse and spine density.
  • It enhances excitatory synaptic transmission and long-term potentiation.
  • NDE2 significantly impacts hippocampal-dependent memory, including recognition, spatial, and contextual fear memory.

Conclusions:

  • NDE2 is a key neuromodulator essential for synaptic plasticity and memory.
  • It exerts its effects via estrogen receptor signaling, impacting kinase and CREB-BDNF pathways.
  • These pathways regulate synaptic protein dynamics critical for learning and memory.