Impact of dopaminergic alterations on the hypothalamic-pituitary-adrenal axis in translational Alzheimer's disease models.

The project investigates how early alterations of the dopaminergic system in Alzheimer's disease can influence the hypothalamic-pituitary-adrenal axis, leading to chronic peripheral inflammation. Using translational murine models, the research will combine retrograde tracing techniques with histological and molecular biology analyses. The three main objectives are: 1) to determine the neuronal circuit connecting the ventral tegmental area to the paraventricular nucleus of the hypothalamus; 2) to evaluate the impact of dopaminergic depletion on hypothalamic neurons; and 3) to verify whether and how this chronic deficit can induce peripheral inflammation. The expected outcome is the definition of a circuit and mechanistic framework linking mesencephalic dopaminergic neurodegeneration to the systemic inflammation typical of Alzheimer’s Disease.