Intravital characterization of mitochondrial dysfunction in the aged brain endothelium
The human brain accounts for only 2% of total body mass but requires 20-25% of the body's energy. Energy supply to the brain is regulated through neurovascular coupling (NVC), a process involving intercellular signaling between neurons and microvascular endothelial cells. These cells play a crucial role in maintaining brain homeostasis through their regulation of vasoactive mediators and reactive oxygen species production. In aging, mitochondrial dysfunction can lead to NVC impairment, blood-brain barrier damage, and potential neuronal degeneration. This project aims to understand the impact of age-related changes in brain endothelial mitochondrial function in on neuro-glial-vascular unit function and angiogenic capacity. The study will use novel fluorescent biosensors, metabolic flux analysis, high-resolution respirometry, two-photon microscopy, and ultrafast ultrasound in mice models to monitor metabolic changes in the cerebrovascular system in vivo.
