The role of 17beta-estradiol on pilocarpine-induced epilepsy and the downregulation of hippocampal membrane GluR2 and HCN1 channel protein levels in ovariectomized mice
| Project/Area Number |
25430070
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Neurochemistry/Neuropharmacology
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| Research Institution | Ohu University |
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Principal Investigator |
SEKI Kenjiro 奥羽大学, 薬学部, 講師 (50342803)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| 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 / 月経随伴性てんかん発作 / エストロゲン / 海馬 / ピロカルピン / HCN1チャネル / AMPA-GluR2 / てんかん発作 / AMPA受容体 / シグナル伝達系 / HCNチャネル / GluR2 / 細胞内トラフィッキング / マウス |
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| 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.
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Report
(4 results)
Research Products
(3 results)
