Amyloid P oligomer promotes microglial galectin-3 and astrocytic lipocalin-2 levels in the hippocampus of mice fed a high-fat diet

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 (APO) 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 APO. Sholl analysis of iba-1-positive microglia showed retraction of microglial ramifications in the hippocampus of HFD-fed diabetic mice. APO 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 APO treatment. These findings suggest that galectin-3 and LCN2 are involved in amyloid toxicity mechanisms, especially glial activation under diabetic conditions. (c) 2023 Elsevier Inc. All rights reserved.