The concept that estradiol may act as a local neuromodulator in the brain, rapidly affecting connectivity and synaptic function, has been firmly established by research over the last 30 years. De novo synthesis of estradiol within the brain as well as signaling mechanisms mediating responses to the hormone have been demonstrated, along with morphological evidence indicating rapid changes in synaptic input following increases in local estradiol levels. These rapid synaptic effects may play important roles in both physiological and pathophysiological responses to changes in circulating hormone levels, as well as in neurodegenerative disease. How local effects of estradiol on synaptic plasticity are integrated into changes in the overall activity of neural networks in the brain, however, remains a subject that is only incompletely understood.
Keywords: AMPA receptors; Electron microscopic stereology; Estrogen receptors; Gonadal hormones; Hippocampus; NMDA receptors; Neurodegenerative diseases; Prefrontal cortex; Spine synapses.
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