Our group is devoted to understanding how the metabolic flexibility of astrocytes impact on neuronal function and organismal higher-order behaviors. The brain has almost no energy reserve but its activity coordinates organismal function, a burden that requires precise coupling between neurotransmission and energy metabolism. Deciphering how the brain accomplishes this complex task is crucial to understand central facets of human physiology and disease mechanisms.

Each type of neural cell displays a peculiar metabolic signature, forcing the intercellular exchange of metabolites that serve as both energy precursors and paracrine signals. The paradigm of this biological feature is the astrocyte-neuron couple, in which the glycolytic metabolism of astrocytes contrasts with the mitochondrial oxidative activity of neurons. Disruption of this metabolic cooperation may contribute to the initiation or progression of several neurological diseases, thus requiring innovative therapies to preserve brain energetics.

Recently we have observed that, besides glucose, astrocytes avidly use fatty acids via mitochondrial ß-oxidation, a feature that allow these cells to keep mitochondrial complex I partially disassembled from complex III. By maintaining this conformation of the mitochondrial respiratory chain, fatty acids utilization in astrocytes allows enhanced mitochondrial reactive oxygen species (mROS) to drive neuronal functions via the modulation of specific molecular targets.

By combining genetic, biochemical and behavioral approaches, our laboratory is therefore dedicated to deciphering the molecular players involved in the regulation of brain cells metabolism that impact on organismal behaviors in health and disease.