Estrogen receptor ß activity modulates synaptic signaling and structure.

ABSTRACT: Brain-synthesized estrogen has been shown to influence synaptic structure, function, and cognitive processes. However, the molecular mechanisms underlying the rapid effects of estrogen on the dendritic spines of cortical neurons are not clear. Estrogen receptor ? (ER?) is expressed in cortical neurons, and ER? knock-out mice display impaired performance in cortically mediated processes, suggesting that signaling via this receptor has profound effects on cortical neuron function. However, the effect of rapid signaling via ER? on dendritic spines and the signaling pathways initiated by this receptor in cortical neurons are unknown. Here, we show that activation of ER? with the specific agonist WAY-200070 results in increased spine density and PSD-95 (postsynaptic density-95) accumulation in membrane regions. Activation of ER? by WAY-200070 also resulted in the phosphorylation of p21-activated kinase (PAK) and extracellular signal-regulated kinase 1/2 (ERK1/2) in cultured cortical neurons, suggesting a mechanism for the regulation of the actin cytoskeleton. Moreover, we found that aromatase, an enzyme critical for estrogen production, is present at presynaptic termini, supporting a role for brain-synthesized estrogen as a neuromodulator in the cortex. These results implicate ER? signaling in controlling dendritic spine morphology, in part via a PAK/ERK1/2-dependent pathway, and provide mechanistic insight into the rapid cellular effects of estrogen on brain function.

SUBMITTER: Srivastava DP 

PROVIDER: S-EPMC2956485 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature