Characterization of brain metabolism in a mouse model of Alzheimer's Disease using MALDI-TOF imaging mass spectrometry
Abstract
Alzheimer’s Disease (AD) is the most common form of dementia with no effective therapies to currently prevent or slow its progression. Increasing research into cerebral energy metabolism has revealed the importance of lactate as an energy substrate and signaling molecule required during neuronal activation and memory formation, normal physiological glial function, and the regulation of gene transcription through a novel epigenetic process termed histone lactylation. In this study, I spatially and temporally mapped lactate levels and histone lactylation in brain tissues of wild type and an AD transgenic mouse model using MALDI-TOF imaging mass spectrometry and immunofluorescence microscopy, respectively. Lactate levels declined with age predominantly in male but not female mice. The spatial relationship between lactate levels and histone lactylation suggest that both processes may contribute to microglia activation and neuroinflammation, but the need for cell-type and region-specific investigation is required to further understand the relationship between lactate metabolism and epigenetic processes during aging and in AD.