Manganese-Induced STING Activation Orchestrates Microglial Reprogramming and Cognitive Deficits via HK-2 Targeting

Manganese is an essential trace element, but excessive exposure can cause neurotoxicity and impair learning and memory abilities. Microglia, as the innate immune cells of the central nervous system, their functional reprogramming (especially the shift of energy metabolism to glycolysis) and neuroinflammation play a crucial role in manganese-induced cognitive impairment. The STING signaling pathway may participate in this process by regulating the energy metabolism and inflammatory response of microglia, although the mechanism remains unclear. The study used C57BL/6 mice and BV2 microglial cell models, setting up different manganese exposure groups and the STING inhibitor H151 intervention group. The collected data included: new object recognition, behavioral indicators of Morris water maze; IBA1 immunohistochemistry, Western blot detection of microglial cell activation; Golgi staining to observe changes in synaptic spines; ELISA to detect inflammatory factors; mitochondrial membrane potential, network analysis and ATP/lactic acid detection to evaluate energy metabolism; Western blot detection of STING pathway protein expression. Independent variables: manganese exposure dose, H151 intervention dependent variables: learning and memory ability, microglial cell activation level, synaptic morphology, inflammatory factor level, mitochondrial function indicators, STING pathway protein expression