Estrogen Matters: The Impact of Neuron-Derived Estradiol Katrina Wugalter
While estrogen is necessary for female sexual development, recent research has found that it may also impact certain areas of the brain. Neuroimaging research and neuropsychological tests have revealed that the hippocampus may be an important region of estrogen function. Additionally, studies with ovariectomized animals or post-menopausal women have shown associations between estrogen loss, cognitive decline, and reductions in hippocampal volumes. Researchers have proposed that the reduction of circulating estrogens post-menopause may explain the high prevalence of Alzheimer’s Disease in older women. An interesting finding that complicates estrogen’s effects is the neural production of 17B-estradiol by the aromatase enzyme, found in animals and humans. The recent paper by Lu et al. (2019) utilized a forebrain-specific aromatase knockout mouse model to investigate the impact of neuron-derived estrogen on learning, memory, neural transmission, kinase and neurotrophic signalling, and synaptic plasticity. Their results indicated that loss of neuron-derived estradiol led to reductions in hippocampal-dependent cognitive performance, excitatory transmission, and long-term potentiation induction. The knockout mice also had lower concentrations of phosphorylated kinases and brain-derived neurotrophic factor. Exogenous estradiol treatment in vivo “rescued” the deficits in kinase and neurotrophic signalling, and spatial learning and memory, while in vitro addition of estradiol to hippocampal slices recovered long-term potentiation induction. The researchers conclude that neuron-derived estradiol is a key component of synaptic plasticity and memory and may act through kinases and neurotrophic factors. The limitations of this paper and future directions for the field are discussed.
Key words: estrogen, estradiol, synaptic plasticity, hippocampus, menopause, aromatase, estrogen receptors, hormone replacement therapy
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