Insulin modulates hippocampally-mediated spatial working memory via glucose transporter-4.
Insulin modulates hippocampally-mediated spatial working memory via glucose transporter-4.
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DOI：
10.1016/j.bbr.2017.09.033
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发表时间：
2018-02-15
影响因子：
2.7
通讯作者：
McNay EC
中科院分区：
文献类型：
--
作者：
Pearson-Leary J;Jahagirdar V;Sage J;McNay EC
胰岛素调节的葡萄糖转运蛋白GluT4是外周胰岛素信号传导的关键分子。尽管GluT4在海马等特定脑区神经元中大量表达，但神经元GluT4的功能作用尚不清楚。在这里，我们通过对GluT4介导的葡萄糖摄取的药理抑制来确定GluT4是否在海马中介导胰岛素介导的葡萄糖摄取。与之前的报道一致，我们发现雄性大鼠在自发交替（SA）过程中，海马介导的空间工作记忆任务中，海马背侧的葡萄糖利用增加。我们之前的研究表明，海马体内的胰岛素信号是处理这一任务所必需的，并且外源性胰岛素的管理可以提高表现。在海马胰岛素基线水平下，抑制glut4介导的葡萄糖摄取并不影响SA的表现。然而，抑制GluT4的上游调节因子Akt确实会损害SA的表现。相反，当记忆增强剂量的胰岛素在sa测试前传递到海马体时，抑制glut4介导的葡萄糖运输会阻止认知增强。这些数据表明，基线海马认知处理不需要功能性海马GluT4，但超基线胰岛素的认知增强需要。与这些发现一致，我们发现在神经元细胞培养中，胰岛素以glut4依赖的方式增加葡萄糖利用。总之，这些数据证明了GluT4在转导海马胰岛素升高的前认知效应中的关键作用。
The insulin-regulated glucose transporter, GluT4, is a key molecule in peripheral insulin signaling. Although GluT4 is abundantly expressed in neurons of specific brain regions such as the hippocampus, the functional role of neuronal GluT4 is unclear. Here, we used pharmacological inhibition of GluT4-mediated glucose uptake to determine whether GluT4 mediates insulin-mediated glucose uptake in the hippocampus. Consistent with previous reports, we found that glucose utilization increased in the dorsal hippocampus of male rats during spontaneous alternation (SA), a hippocampally-mediated spatial working memory task. We previously showed that insulin signaling within the hippocampus is required for processing this task, and that administration of exogenous insulin enhances performance. At baseline levels of hippocampal insulin, inhibition of GluT4-mediated glucose uptake did not affect SA performance. However, inhibition of an upstream regulator of GluT4, Akt, did impair SA performance. Conversely, when a memory-enhancing dose of insulin was delivered to the hippocampus prior to SA-testing, inhibition of GluT4-mediated glucose transport prevented cognitive enhancement. These data suggest that baseline hippocampal cognitive processing does not require functional hippocampal GluT4, but that cognitive enhancement by supra-baseline insulin does. Consistent with these findings, we found that in neuronal cell culture, insulin increases glucose utilization in a GluT4-dependent manner. Collectively, these data demonstrate a key role for GluT4 in transducing the procognitive effects of elevated hippocampal insulin.
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影响因子：
16.2
作者：
Fanselow, Michael S.;Dong, Hong-Wei
通讯作者：
Dong, Hong-Wei
影响因子：
7.7
作者：
Alquier, Thierry;Leloup, Corinne;Penicaud, Luc
通讯作者：
Penicaud, Luc
DOI：
10.1016/s0163-1047(86)90626-6
发表时间：
1986-09-01
期刊：
BEHAVIORAL AND NEURAL BIOLOGY
影响因子：
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作者：
GOLD, PE;VOGT, J;HALL, JL
通讯作者：
HALL, JL
影响因子：
5.7
作者：
Christensen, Dan P.;Dahllof, Mattias;Mandrup-Poulsen, Thomas
通讯作者：
Mandrup-Poulsen, Thomas
影响因子：
25
作者：
Drier, EA;Tello, MK;Yin, JCP
通讯作者：
Yin, JCP