Grant: Project Grant

The brain requires a large amount of oxygen and sugar for its size. As there are little energy stores within the brain, brain cells called neurons call out to nearby brain blood vessels to increases blood flow and bring forth new energy supplies. This process is called "neuro-vascular coupling". When the brain cannot get enough oxygen and glucose from the blood, brain malfunction occurs and if severe enough, brain cells die. Poor brain blood flow is not only a consequence of disease, but is now considered causative for the onset and progression of several conditions such as Alzheimer's, the most common form of dementia. 20 years ago, a type of brain support cells called astrocytes were hailed as the key player translating and relaying increasing in neuron activity to blood vessels to increase blood flow. Yet the exact role of astrocytes under more realistic conditions has been difficult to determine. Our lab has unravelled at least part of this mystery, discovering surprisingly specific contributions from astrocytes, including boosting the blood flow control by neurons and controlling basal blood flow independent of neuronal activity. Our new data expand greatly on this view, now supporting the involvement astrocytes in brain blood flow regulation during animal running and sleep, as well as provide new mechanisms for how astrocytes contribute to basal blood flow control. We also find that astrocyte effects become dysregulated in the presence of amyloid beta, a toxic protein found in Alzheimer's disease. Here, we will test that astrocytes regulate components of brain blood flow in specific states (running, sleep, awake but resting), which become impaired in Alzheimer's. We will use cutting-edge imaging and genetic tools to test this central idea. In furthering our discovers on how astrocytes regulated brain blood flow in health and in Alzheimer's disease, we will provide new critical knowledge in this important area of research.