The role of 17beta-estradiol on pilocarpine-induced epilepsy and the downregulation of hippocampal membrane GluR2 and HCN1 channel protein levels in ovariectomized mice

2015 Fiscal Year Final Research Report

• Project/Area Number: 25430070
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: Ohu University
• Principal Investigator: SEKI Kenjiro 奥羽大学, 薬学部, 講師 (50342803)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: シナプス可塑性 / 脳神経疾患 / 興奮性－抑制性神経バランス / 精神疾患

Outline of Final Research Achievements

Estrogen is thought to be a risk factor for catamenial epilepsy E2 significantly increased seizure severity. In this study, we found that the E2 prolonged the latency to status epilepticus (SE) and reduced mortality. Pilocarpine-induced epilepsy reduced the protein level of the AMPA receptor GluR2 subunit at the plasma membrane. However, E2 suppressed this reduction in GluR2 and inhibited Ser880 phosphorylation during epilepsy. Next, we attempted to block GluR2-lacking AMPA receptors via intraventricular administration of 1-Naphthylacetyl spermine (Naspm) to mimic the effects of E2 treatment in freely moving mice. Treatment of Naspm after pilocarpine injection at 3 min, the latency to SE was increased and mortality was reduced. This timing of the effects of Naspm is consistent with the onset of the GluR2 phosphorylation. These results suggest that E2 promotes survival by inhibiting the GluR2 internalization.

Free Research Field

興奮性神経と抑制性神経のバランスの変化及びシナプス可塑性の変化と脳神経疾患