TY - JOUR
T1 - Estrogen receptor β activity modulates synaptic signaling and structure
AU - Srivastava, Deepak P.
AU - Woolfrey, Kevin M.
AU - Liu, Feng
AU - Brandon, Nicholas J.
AU - Penzes, Peter
PY - 2010/10/6
Y1 - 2010/10/6
N2 - 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 β (ERβ) is expressed in cortical neurons, and ERβ 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 ERβ on dendritic spines and the signaling pathways initiated by this receptor in cortical neurons are unknown. Here, we show that activation of ERβ with the specific agonist WAY-200070 results in increased spine density and PSD-95 (postsynaptic density-95) accumulation in membrane regions. Activation of ERβ 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 ERβ 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.
AB - 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 β (ERβ) is expressed in cortical neurons, and ERβ 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 ERβ on dendritic spines and the signaling pathways initiated by this receptor in cortical neurons are unknown. Here, we show that activation of ERβ with the specific agonist WAY-200070 results in increased spine density and PSD-95 (postsynaptic density-95) accumulation in membrane regions. Activation of ERβ 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 ERβ 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.
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U2 - 10.1523/JNEUROSCI.3264-10.2010
DO - 10.1523/JNEUROSCI.3264-10.2010
M3 - Article
C2 - 20926671
AN - SCOPUS:77957734474
SN - 0270-6474
VL - 30
SP - 13454
EP - 13460
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 40
ER -