The progesterone-induced enhancement of object recognition memory consolidation involves activation of the extracellular signal-regulated kinase (ERK) and mammalian target of rapamycin (mTOR) pathways in the dorsal hippocampus.
The progesterone-induced enhancement of object recognition memory consolidation involves activation of the extracellular signal-regulated kinase (ERK) and mammalian target of rapamycin (mTOR) pathways in the dorsal hippocampus.
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DOI：
10.1016/j.yhbeh.2012.01.004
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发表时间：
2012-04
影响因子：
3.5
通讯作者：
Frick, Karyn M.
中科院分区：
文献类型：
--
作者：
Orr, Patrick T.;Rubin, Amanda J.;Fan, Lu;Kent, Brianne A.;Frick, Karyn M.
虽然最近的研究已经阐明了17β-雌二醇调节记忆的生化机制，但对孕酮（P）调节记忆的信号传导事件知之甚少。我们最近证明，立即培训后注入P到背海马增强对象识别记忆巩固年轻的卵巢切除雌性小鼠。本研究的目的是确定可能导致这种记忆增强的生化改变。我们假设P诱导的物体识别增强依赖于ERK和mTOR通路的激活。在年轻的卵巢切除小鼠中，我们发现双侧背海马输注P显著增加了输注后5分钟背海马中磷酸化p42 ERK和mTOR底物S6 K的水平。输注后15分钟磷酸化p42 ERK水平下调，输注后30分钟恢复至基线水平，表明P对ERK激活的双相作用。背侧海马ERK和mTOR激活是必要的P，以促进记忆巩固，这两个途径的抑制剂注入背侧海马训练后立即阻止P-诱导的增强物体识别的事实表明。总的来说，这些数据提供了第一个证明，P增强记忆巩固的能力取决于背海马中细胞信号传导和蛋白质合成途径的快速激活。
Although much recent work has elucidated the biochemical mechanisms underlying the modulation of memory by 17β-estradiol, little is known about the signaling events through which progesterone (P) regulates memory. We recently demonstrated that immediate post-training infusion of P into the dorsal hippocampus enhances object recognition memory consolidation in young ovariectomized female mice. The goal of the present study was to identify the biochemical alterations that might underlie this mnemonic enhancement. We hypothesized that the P-induced enhancement of object recognition would be dependent on activation of the ERK and mTOR pathways. In young ovariectomized mice, we found that bilateral dorsal hippocampal infusion of P significantly increased levels of phospho-p42 ERK and the mTOR substrate S6K in the dorsal hippocampus 5 minutes after infusion. Phospho-p42 ERK levels were downregulated 15 minutes after infusion and returned to baseline 30 minutes after infusion, suggesting a biphasic effect of P on ERK activation. Dorsal hippocampal ERK and mTOR activation were necessary for P to facilitate memory consolidation, as suggested by the fact that inhibitors of both pathways infused into the dorsal hippocampus immediately after training blocked the P-induced enhancement of object recognition. Collectively, these data provide the first demonstration that the ability of P to enhance memory consolidation depends on the rapid activation of cell signaling and protein synthesis pathways in the dorsal hippocampus.
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DOI：
10.1111/j.1749-6632.2010.05529.x
发表时间：
2010-01-01
期刊：
REPRODUCTIVE AGING
影响因子：
--
作者：
Dumitriu, Dani;Rapp, Peter R.;Morrison, John H.
通讯作者：
Morrison, John H.
影响因子：
2.7
作者：
Bekinschtein, Pedro;Katche, Cynthia;Medina, Jorge H.
通讯作者：
Medina, Jorge H.
影响因子：
2.9
作者：
BITRAN, D;HILVERS, RJ;KELLOGG, CK
通讯作者：
KELLOGG, CK
影响因子：
3.8
作者：
BREWSTER, ME;ANDERSON, WR;POP, E
通讯作者：
POP, E
影响因子：
1.9
作者：
BITRAN, D;HILVERS, RJ;KELLOGG, CK
通讯作者：
KELLOGG, CK