TLR4 依赖性代谢变化与 1 型糖尿病动物模型认知障碍有关。
TLR4-dependent metabolic changes are associated with cognitive impairment in an animal model of type 1 diabetes.
机构信息
Laboratory of Neurosciences, National Institute on Aging, Intramural Research Program, National Institutes of Health, Baltimore, MD, USA.
Laboratory of Neurosciences, National Institute on Aging, Intramural Research Program, National Institutes of Health, Baltimore, MD, USA; Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
出版信息
Biochem Biophys Res Commun. 2014 Jan 10;443(2):731-7. doi: 10.1016/j.bbrc.2013.12.039. Epub 2013 Dec 14.
We investigated the role of Toll-like receptor 4 (TLR4), a major mediator of innate immune responses, on cognitive performance in a type 1 diabetes model (T1D). After administration of streptozotocin, both TLR4 knockout (TLR4 KO) and wild type (WT) diabetic mice displayed metabolic alterations similar to those observed in T1D patients, including increased levels of glucose, cholesterol, triglycerides and ketones. T1D mice exhibited cognitive impairment which was less severe in TLR4 KO mice compared to WT mice. WT mice with higher glucose and those with higher triglyceride levels exhibited significantly more anxiety and impaired memory compared to those with lower levels of glucose and triglycerides; these correlations were absent in TLR4 KO mice. Additional findings suggest roles for TLR4 signaling in modifying the expression of enzymes involved in energy metabolism in brain cells in the setting of T1D. Our data show that TLR4 contributes to the negative impact of T1D on anxiety and cognition.
我们研究了 Toll 样受体 4（TLR4）在 1 型糖尿病模型（T1D）中对认知功能的作用，TLR4 是先天免疫反应的主要介质。在给予链脲佐菌素后，TLR4 敲除（TLR4 KO）和野生型（WT）糖尿病小鼠均表现出与 T1D 患者相似的代谢改变，包括葡萄糖、胆固醇、甘油三酯和酮体水平升高。T1D 小鼠表现出认知障碍，与 WT 小鼠相比，TLR4 KO 小鼠的认知障碍程度较轻。与葡萄糖和甘油三酯水平较低的小鼠相比，葡萄糖和甘油三酯水平较高的 WT 小鼠表现出明显更多的焦虑和记忆障碍；而在 TLR4 KO 小鼠中，这些相关性并不存在。其他研究结果表明，TLR4 信号在调节 T1D 情况下脑细胞中参与能量代谢的酶的表达方面发挥作用。我们的数据表明，TLR4 导致 T1D 对焦虑和认知产生负面影响。
Zotero 插件