Reduced Cyclic Adenosine Monophosphate Level in Hippocampal CA1 Participates in Propofol Induced Amnesia in Rats.
Reduced Cyclic Adenosine Monophosphate Level in Hippocampal CA1 Participates in Propofol Induced Amnesia in Rats.
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海马 CA1 环磷酸腺苷水平降低参与异丙酚诱导的大鼠遗忘症
DOI：
10.3389/fnins.2018.00337
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发表时间：
2018
影响因子：
4.3
通讯作者：
Xu H
中科院分区：
文献类型：
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作者：
Li W;Yu L;Yan X;Cai L;Wan L;Teng Q;Li Y;Wang Y;Xu H
异丙酚抑制海马CA1区的长时程增强（LTP），并阻碍情节记忆的形成。然而，异丙酚作用的分子机制仍然知之甚少。已有研究表明，异丙酚抑制cAMP反应元件结合蛋白信号通路，可能与大鼠记忆障碍有关。在此，我们首次证明了丙泊酚灌注可以抑制forskolin诱导的大鼠海马CA1脑片LTP。异丙酚还降低cAMP水平，这可以被非选择性PDE抑制剂IBMX逆转。我们进一步发现丙泊酚可增加海马CA1区PDE4活性和PDE4AX蛋白表达。PDE4抑制剂咯利普兰预处理可减轻丙泊酚对大鼠海马CA1区LTP的抑制作用和对海马依赖性记忆形成的损害。因此，我们的研究结果表明，通过增加PDE4活性和PDE4AX蛋白在海马CA1区的表达降低cAMP水平在丙泊酚诱导的遗忘中起着重要作用。
Propofol inhibits long-term potentiation (LTP) in the hippocampal CA1 region and impedes episodic memory formation. However, the molecular mechanisms involved in the effect of propofol are still poorly understood. It had been reported that propofol inhibited cAMP response element binding protein signaling, which was proposed to contribute to memory retention impairment in rats. Here, we first demonstrated that propofol perfusion could inhibit forskolin induced LTP in the rat hippocampal CA1 slices. Propofol also reduced the level of cAMP, which could be reversed by non-selective PDE inhibitor IBMX. We further discovered that propofol could increase both PDE4 activity and PDE4AX protein expressions in the hippocampal CA1 region. Furthermore, pretreatment of rolipram, a PDE4 inhibitor, rescued propofol induced inhibition of CA1 LTP and the impairment of hippocampus-dependent memory formation in rats. Thus, our results suggest that reduced levels of cAMP by increasing PDE4 activity and PDE4AX protein expressions in the hippocampal CA1 region plays an important role in the propofol-induced amnesia.
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影响因子：
2.4
作者：
Kida S
通讯作者：
Kida S
影响因子：
4
作者：
Miller, S;Mayford, M
通讯作者：
Mayford, M
影响因子：
8.8
作者：
Ren, Yu;Zhang, Fu-Jun;Yu, Bu-Wei
通讯作者：
Yu, Bu-Wei
影响因子：
2
作者：
Nguyen, PV;Kandel, ER
通讯作者：
Kandel, ER
影响因子：
64.8
作者：
通讯作者：
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