High-fat diet increases gliosis and immediate early gene expression in APOE3 mice, but not APOE4 mice.
High-fat diet increases gliosis and immediate early gene expression in APOE3 mice, but not APOE4 mice.
复制标题
DOI：
10.1186/s12974-021-02256-2
复制
发表时间：
2021-09-18
影响因子：
9.3
通讯作者：
Rebeck GW
中科院分区：
文献类型：
--
作者：
Jones NS;Watson KQ;Rebeck GW
载脂蛋白E4是阿尔茨海默病(AD)最强的遗传风险因素，肥胖是AD的强烈环境风险因素。这些因素会导致多个中枢神经系统(CNS)紊乱，并显著增加患AD的几率。由于超过20%的美国人携带APOE4等位基因，超过40%的人肥胖，了解这些危险因素是如何相互作用影响中枢神经系统中的神经元和神经胶质细胞是很重要的。从6个月大开始，我们给雄性和雌性APOE3和APOE4基因敲除小鼠喂高脂饮食(HFD-45%千卡脂肪)或“对照”饮食(CD-10%千卡脂肪)，为期12周。在12周结束时，收集大脑并分析神经胶质增生、神经炎性基因和神经元完整性。通过GFAP和Iba1免疫染色，服用HFD的APOE3小鼠，而不是APOE4小鼠，经历了胶质细胞增生症的增加。ApoE4组较APOE3组Adora2a的表达增加更明显。最后，服用HFD的APOE3小鼠，而不是APOE4小鼠，也显示出即刻早期基因CFos和Arc在神经元中的表达增加。这些发现表明，APOE基因型和肥胖在重要的过程中相互作用，特别是与中枢神经系统的炎症和神经元可塑性有关的过程。在肥胖的早期阶段，APOE3型调节对HFD的反应，而APOE4型不调节。这支持了一种模型，即APOE4大脑中早期炎症调节失调可能容易导致各种侮辱对中枢神经系统的损害，并在以后导致通常与APOE4基因相关的中枢神经系统损害增加。
APOE4 is the strongest genetic risk factor for Alzheimer’s disease (AD), and obesity is a strong environmental risk factor for AD. These factors result in multiple central nervous system (CNS) disturbances and significantly increase chances of AD. Since over 20% of the US population carry the APOE4 allele and over 40% are obese, it is important to understand how these risk factors interact to affect neurons and glia in the CNS. We fed male and female APOE3 and APOE4 knock-in mice a high-fat diet (HFD-45% kcal fat) or a "control" diet (CD-10% kcal fat) for 12 weeks beginning at 6 months of age. At the end of the 12 weeks, brains were collected and analyzed for gliosis, neuroinflammatory genes, and neuronal integrity. APOE3 mice on HFD, but not APOE4 mice, experienced increases in gliosis as measured by GFAP and Iba1 immunostaining. APOE4 mice on HFD showed a stronger increase in the expression of Adora2a than APOE3 mice. Finally, APOE3 mice on HFD, but not APOE4 mice, also showed increased neuronal expression of immediate early genes cFos and Arc. These findings demonstrate that APOE genotype and obesity interact in their effects on important processes particularly related to inflammation and neuronal plasticity in the CNS. During the early stages of obesity, the APOE3 genotype modulates a response to HFD while the APOE4 genotype does not. This supports a model where early dysregulation of inflammation in APOE4 brains could predispose to CNS damages from various insults and later result in the increased CNS damage normally associated with the APOE4 genotype.
登录
查看更多内容
影响因子：
12.4
作者：
Boison, D.;Chen, J-F;Fredholm, B. B.
通讯作者：
Fredholm, B. B.
载脂蛋白E4介导与胰岛素抵抗相关的脑血管功能障碍和餐后反应。
DOI：
10.1177/0271678x17746186
发表时间：
2019-05
期刊：
Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
影响因子：
--
作者：
Johnson LA;Torres ER;Weber Boutros S;Patel E;Akinyeke T;Alkayed NJ;Raber J
通讯作者：
Raber J
影响因子：
5.2
作者：
Huebbe, Patricia;Dose, Janina;Rimbach, Gerald
通讯作者：
Rimbach, Gerald
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：
Dinel AL;André C;Aubert A;Ferreira G;Layé S;Castanon N
通讯作者：
Castanon N