TY - JOUR
T1 - Endogenous 17β-estradiol is required for activity-dependent long-term potentiation in the striatum
T2 - Interaction with the dopaminergic system
AU - Tozzi, Alessandro
AU - de Iure, Antonio
AU - Tantucci, Michela
AU - Durante, Valentina
AU - Quiroga-Varela, Ana
AU - Giampà, Carmela
AU - Di Mauro, Michela
AU - Mazzocchetti, Petra
AU - Costa, Cinzia
AU - Di Filippo, Massimiliano
AU - Grassi, Silvarosa
AU - Pettorossi, Vito Enrico
AU - Calabresi, Paolo
PY - 2015/5/27
Y1 - 2015/5/27
N2 - 17β-estradiol (E2), a neurosteroid synthesized by P450-aromatase (ARO), modulates various brain functions. We characterized the role of the locally synthesized E2 on striatal long-term synaptic plasticity and explored possible interactions between E2 receptors (ERs) and dopamine (DA) receptors in the dorsal striatum of adult male rats. Inhibition of E2 synthesis or antagonism of ERs prevented the induction of long-term potentiation (LTP) in both medium spiny neurons (MSNs) and cholinergic interneurons (ChIs). Activation of a D1-like DA receptor/cAMP/PKA-dependent pathway restored LTP. In MSNs exogenous E2 reversed the effect of ARO inhibition. Also antagonism of M1 muscarinic receptors prevented the D1-like receptor-mediated restoration of LTP confirming a role for ChIs in controlling the E2-mediated LTP of MSNs. A novel striatal interaction, occurring between ERs and D1-like receptors in both MSNs and ChIs, might be critical to regulate basal ganglia physiology and to compensate synaptic alterations in Parkinson’s disease.
AB - 17β-estradiol (E2), a neurosteroid synthesized by P450-aromatase (ARO), modulates various brain functions. We characterized the role of the locally synthesized E2 on striatal long-term synaptic plasticity and explored possible interactions between E2 receptors (ERs) and dopamine (DA) receptors in the dorsal striatum of adult male rats. Inhibition of E2 synthesis or antagonism of ERs prevented the induction of long-term potentiation (LTP) in both medium spiny neurons (MSNs) and cholinergic interneurons (ChIs). Activation of a D1-like DA receptor/cAMP/PKA-dependent pathway restored LTP. In MSNs exogenous E2 reversed the effect of ARO inhibition. Also antagonism of M1 muscarinic receptors prevented the D1-like receptor-mediated restoration of LTP confirming a role for ChIs in controlling the E2-mediated LTP of MSNs. A novel striatal interaction, occurring between ERs and D1-like receptors in both MSNs and ChIs, might be critical to regulate basal ganglia physiology and to compensate synaptic alterations in Parkinson’s disease.
KW - Cholinergic interneurons
KW - D1 receptor
KW - Estrogen receptors
KW - Long-term potentiation
KW - Medium spiny neurons
KW - P450-aromatase
KW - Striatum
KW - Synaptic plasticity
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U2 - 10.3389/fncel.2015.00192
DO - 10.3389/fncel.2015.00192
M3 - Article
AN - SCOPUS:84930506249
VL - 9
JO - Frontiers in Cellular Neuroscience
JF - Frontiers in Cellular Neuroscience
SN - 1662-5102
IS - MAY
M1 - 192
ER -