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Estrogen synthesis in the brain--role in synaptic plasticity and memory
Yasushi Hojo1, Gen Murakami, Hideo Mukai
1Department of Biophysics and Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, Komaba, Meguro, Tokyo 153-8902, Japan.
Molecular and Cellular Endocrinology
|June 11, 2008
Summary
Neurosteroids like estrogen and androgen are synthesized in the hippocampus, rapidly influencing memory and synaptic plasticity through specific receptors. This local synthesis impacts neuronal function, particularly in memory-related processes.
Area of Science:
- Neuroendocrinology
- Neurosteroidogenesis
- Synaptic Plasticity
Background:
- Neurosteroids, including estrogen and androgen, are synthesized locally within hippocampal neurons from cholesterol.
- Enzymes like cytochrome P450s, hydroxysteroid dehydrogenases (HSDs), and 5alpha-reductase facilitate neurosteroid synthesis in the hippocampus.
- Despite lower expression than in endocrine organs, enzyme levels are sufficient for significant local neurosteroid production.
Purpose of the Study:
- To investigate the local synthesis and functional role of neurosteroids in the adult hippocampus.
- To elucidate the rapid effects of estrogen on memory-related synaptic plasticity, including spinogenesis and long-term depression (LTD).
- To determine the specific estrogen receptor subtypes involved in mediating these rapid neurosteroid actions.
Main Methods:
- Localization studies of key neurosteroidogenic enzymes (P450(17alpha), P450arom, 17beta-HSD, 5alpha-reductase) in hippocampal neurons.
- Measurement of endogenous estrogen and androgen levels in the hippocampus.
- Electrophysiological and morphological analyses to assess the impact of 17beta-estradiol on synaptic plasticity (LTD) and spine density.
Main Results:
- Neurosteroidogenic enzymes are localized in principal glutamatergic neurons in the hippocampus (CA1, CA3, dentate gyrus).
- Several nanomolar concentrations of estrogen and androgen are detected in the hippocampus.
- Rapid (within 1-2 hours) modulation of LTD and spinogenesis by 17beta-estradiol was observed, with region-specific effects on spine density (increase in CA1, decrease in CA3).
Conclusions:
- The adult hippocampus possesses the machinery for local synthesis of estrogen and androgen.
- Estrogen exerts rapid, receptor-mediated effects on hippocampal synaptic plasticity and neuronal morphology, influencing memory processes.
- Estrogen receptor alpha (ERalpha) mediates these rapid effects on spinogenesis and LTD, highlighting its critical role in neurosteroid signaling within the hippocampus.
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