Irs2 deficiency alters hippocampus-associated behaviors during young adulthood.
Irs2 deficiency alters hippocampus-associated behaviors during young adulthood.
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DOI：
10.1016/j.bbrc.2021.04.101
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发表时间：
2021-06-25
影响因子：
3.1
通讯作者：
Taguchi A
中科院分区：
文献类型：
--
作者：
Tanokashira D;Wang W;Maruyama M;Kuroiwa C;White MF;Taguchi A
2型糖尿病（T2 DM）以高血糖和胰岛素抵抗为特征，已被认为是认知障碍和痴呆（包括阿尔茨海默病（AD））的危险因素。胰岛素受体底物2（IRS 2）是胰岛素/胰岛素样生长因子-1信号通路的主要组成部分。Irs 2缺失导致危及生命的T2 DM，促进雄性小鼠的过早死亡，无论其遗传背景如何。在这里，我们第一次证明了在C57 BL/6 J遗传背景上缺乏Irs 2的年轻成年雄性小鼠（Irs 2-/-/6 J）在不同的实验环境中存活，并显示出与海马相关的行为改变。年轻的成年雄性Irs 2 −/−/6 J小鼠也表现出能量和营养传感器的异常变化，如AMP活化蛋白激酶（AMPK）和葡萄糖转运蛋白3（GLUT 3），以及核心体温降低，伴随着大脑温度传感器的异常变化。这些结果表明，Irs 2缺陷引起的脑能量代谢和体温调节障碍有助于年轻成年雄性小鼠的海马相关行为变化。
Type 2 diabetes mellitus (T2DM), characterized by hyperglycemia and insulin resistance, has been recognized as a risk factor for cognitive impairment and dementia, including Alzheimer’s disease (AD). Insulin receptor substrate2 (IRS2) is a major component of the insulin/insulin-like growth factor-1 signaling pathway. Irs2 deletion leads to life-threatening T2DM, promoting premature death in male mice regardless of their genetic background. Here, we showed for the first time that young adult male mice lacking Irs2 on a C57BL/6J genetic background (Irs2−/−/6J) survived in different experimental environments and displayed hippocampus-associated behavioral alterations. Young adult male Irs2−/−/6J mice also exhibit aberrant alterations in energy and nutrient sensors, such as AMP-activated protein kinase (AMPK) and glucose transporter3 (GLUT3), and reduced core body temperature accompanied by abnormal change in the temperature sensor in the brain. These results suggest that Irs2 deficiency-induced impairments of brain energy metabolism and thermoregulation contribute to hippocampus-associated behavioral changes in young adult male mice.
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影响因子：
11
作者：
Takayanagi Y;Ishizuka K;Laursen TM;Yukitake H;Yang K;Cascella NG;Ueda S;Sumitomo A;Narita Z;Horiuchi Y;Niwa M;Taguchi A;White MF;Eaton WW;Mortensen PB;Sakurai T;Sawa A
通讯作者：
Sawa A
影响因子：
6.1
作者：
Arnold SE;Lucki I;Brookshire BR;Carlson GC;Browne CA;Kazi H;Bang S;Choi BR;Chen Y;McMullen MF;Kim SF
通讯作者：
Kim SF
影响因子：
3.7
作者：
Costello DA;Claret M;Al-Qassab H;Plattner F;Irvine EE;Choudhury AI;Giese KP;Withers DJ;Pedarzani P
通讯作者：
Pedarzani P
影响因子：
2.6
作者：
Tanokashira D;Kurata E;Fukuokaya W;Kawabe K;Kashiwada M;Takeuchi H;Nakazato M;Taguchi A
通讯作者：
Taguchi A
影响因子：
64.5
作者：
Ye L;Kleiner S;Wu J;Sah R;Gupta RK;Banks AS;Cohen P;Khandekar MJ;Boström P;Mepani RJ;Laznik D;Kamenecka TM;Song X;Liedtke W;Mootha VK;Puigserver P;Griffin PR;Clapham DE;Spiegelman BM
通讯作者：
Spiegelman BM