Department of Anatomy and Convergence Medical Science, College of Medicine, Institute of Health Sciences, Gyeongsang National University, Jinju, 52727, Republic of Korea.
Department of Anatomy and Convergence Medical Science, College of Medicine, Institute of Health Sciences, Gyeongsang National University, Jinju, 52727, Republic of Korea.
Biochem Biophys Res Commun. 2023 Jul 30;667:10-17. doi: 10.1016/j.bbrc.2023.05.026. Epub 2023 May 8.
Type 2 diabetes is associated with a risk factor for Alzheimer's disease (AD). Activation of glial cells, such as microglia and astrocytes, is crucial for the development of neuroinflammation in both diabetes and AD. The role of amyloid-beta oligomer (AβO) in the hippocampus of diabetic mice has been investigated; however, the effect of galectin-3 and lipocalin-2 (LCN2) on amyloid toxicity-related glial activation in diabetic mice is not known. To fill this knowledge gap, we fed mice a high-fat diet (HFD) for 20 weeks to induce a diabetic state and then injected the hippocampus with AβO. Sholl analysis of iba-1-positive microglia showed retraction of microglial ramifications in the hippocampus of HFD-fed diabetic mice. AβO treatment caused more retraction of microglial process in HFD-fed mice. In particular, microglial galectin-3 levels and astrocytic LCN2 levels were increased in the hippocampus of HFD-fed mice with AβO treatment. These findings suggest that galectin-3 and LCN2 are involved in amyloid toxicity mechanisms, especially glial activation under diabetic conditions.
2 型糖尿病与阿尔茨海默病（AD）的一个危险因素有关。神经胶质细胞（如小胶质细胞和星形胶质细胞）的激活对于糖尿病和 AD 中神经炎症的发展至关重要。已经研究了淀粉样蛋白-β寡聚物（AβO）在糖尿病小鼠海马中的作用；然而，尚不清楚半乳糖凝集素-3 和脂联素-2（LCN2）对糖尿病小鼠与淀粉样毒性相关的神经胶质激活的影响。为了填补这一知识空白，我们用高脂肪饮食（HFD）喂养小鼠 20 周以诱导糖尿病状态，然后在海马中注射 AβO。Iba-1 阳性小胶质细胞的 Sholl 分析显示，HFD 喂养的糖尿病小鼠海马中小胶质细胞的分支回缩。AβO 处理导致 HFD 喂养小鼠小胶质细胞突起回缩更多。特别是，HFD 喂养的小鼠海马中存在 AβO 处理时小胶质细胞半乳糖凝集素-3 和星形胶质细胞脂联素-2 水平升高。这些发现表明，半乳糖凝集素-3 和 LCN2 参与淀粉样蛋白毒性机制，特别是糖尿病条件下的神经胶质激活。
