Brain energy metabolism and regulation of cerebral blood flow

The high metabolic rate of the brain, associated with the activities of billions of nerve cells processing information, requires constant and optimal nutrient and oxygen supply, as well as the effective elimination of metabolic waste products, which is ensured by complex physiological mechanisms controlling systemic and cerebral circulation. Sustained efficacy of these mechanisms maintains neurological health and promotes brain longevity. There is growing evidence that a reduction in blood flow to the brain, resulting in impaired delivery of metabolic substrates, damages nerve cells and the connections between them, leading to cognitive decline and the development of neurodegenerative diseases, such as Alzheimer's disease. We study the fundamental biological processes that ensure the nutritional support of nerve cell activity, effective elimination of carbon dioxide as a major brain waste product, and the mechanisms activated in conditions of metabolic emergency, such as when oxygen supply to the brain is reduced. We investigate how brain blood flow is fine-tuned to support dynamic changes in local neuronal circuit activity and how it is regulated to protect neuronal networks from deleterious changes in carbon dioxide concentration and oxygen availability. This research is supported by the Wellcome Trust.

Autonomic control of the heart during exercise

The brain controls heart function by sending commands through specialized nerves. These brain-heart connections are vital to produce rapid changes in heart rate and determine how hard the heart works, which is essential for our daily activities and especially during physical activity and exercise. The efficacy of communication between the brain and the heart increases as a result of exercise training and contributes to optimizing exercise performance. In contrast, during the development of cardiovascular disease, diabetes, as well as normal aging, the activities of these nerves decline. This impairs communication between the brain and the heart, rendering the heart unable to rapidly respond to changes in behavioral/physical demands and limiting our ability to exercise. Our studies aim to determine the physiological principles underlying adaptive and maladaptive alterations in the efficacy of communication between the brain and the heart that develop in response to exercise training and during the progression of cardiovascular disease. Since maintaining physical activity is essential for every aspect of physical, emotional, and cognitive health, we also aim to identify how these nervous mechanisms can be activated to enhance the ability to exercise, increase quality of life, and promote cardiovascular health across the lifespan. This research is supported by the British Heart Foundation.