Insulin signaling and microglia in the young and aged brain

Since the discovery of insulin as treatment for diabetes, observations showed that diabetic patients have higher chances to develop neurodegenerative disorders as Alzheimer’s disease. The role of insulin in the central nervous system is an important topic of interest in the molecular and cellular neuroscience research field. Microglia are the macrophages of the central nervous system with immunological functions and play an important role in neuroinflammation. Insulin signaling resistance in the aging brain and insulin signaling in astrocytes are more recent findings that broaden the perspective of the role of insulin in the brain. Insulin is an important factor that in addition to astrocytes also affects neurons, and its function can be altered or (partially) lost during life. In the studies presented in this thesis, new molecular and cellular mechanisms of insulin signaling in the hippocampus and its effects on microglia and neuroinflammation in both young and aged brains were identified. New insights into insulin effects on microglia metabolism followed by a new strategy to access microglia oxygen metabolism and mitochondrial function were also objects of study. Present data show that microglia are sensitive to insulin in both cell culture and in vivo with a protective pro-inflammatory effect. Complementarily, it was found that insulin modulates microglia oxygen metabolism and the production of reactive oxygen species in both a mitochondrial-dependent and -independent manner. In this thesis, the inflammatory signaling of insulin and the metabolism of microglia was investigated in the brain