Spatiotemporal imaging of astrocytic fatty acid oxidation and intercellular metabolic fluxes in brain

Metabolic changes play a crucial role in brain plasticity and cognitive functions, with fatty acid oxidative metabolism (FAO) in astrocytes emerging as a pivotal pathway. However, our knowledge of the mechanisms regulating astrocytic FAO and its dysregulation in pathological conditions remains significantly limited. The general aim of our research is to understand key features of brain energetics studying spatiotemporal characteristics of astrocytic FAO and intercellular metabolism fluxes in cerebral cortex and in APOE4 expressing cell models. ApoE4 is the major genetic risk factor of late onset Alzheimers disease. To conduct our research, we will utilize a wide range of experimental approaches such as biochemical, metabolic and omics analyses. We will also perform confocal and super resolution SIM microscopy of 1) metabolic substrate sensors, and 2) mitochondrial and lipid droplet dynamics in rat and human cultured astrocytes, mixed neuron-astrocyte cultures and brain slices. Our proposal is scientifically and socially relevant as we expect to advance in the knowledge of brain metabolism but also to provide important data to uncover potential targets for pharmacological and/or nutritional intervention.