Cholesterol-driven pathological astrocytic responses in diabetes-associated cognitive impairment through astrocytic SCAP accumulation and NF-κB-C3 signaling modulation.

ABSTRACT: The diabetic environment, characterized by hyperglycemia, advanced glycation end products and cerebral insulin resistance, triggers pathological astrocytic responses that contribute to cognitive decline in diabetes-associated cognitive impairment. Cholesterol accumulation in the brain, particularly in astrocytes, contributes to this pathological process. SCAP, a cholesterol sensor involved in lipid imbalances, regulates metabolic diseases, but its role in astrocytes remains unclear. C57BL/6J wild-type and astrocyte-specific SCAP knockout mice were fed a high-fat diet and treated with streptozotocin to induce type 2 diabetes mellitus (T2DM). Behavioral tests and hippocampal histology were performed at 28 weeks. We investigated the NF-κB-C3 signaling pathway to elucidate how SCAP induces pat

SUBMITTER: Niu T 

PROVIDER: S-EPMC12508041 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature