How glial cells safeguard brain energetics, cognition, and resilience to inflammation in health and ageing?
Supervisors:
Shefeeq Theparambil, Department of Biomedical and Life Sciences, Lancaster University
Julia Edgar, Infection & Immunity, University of Glasgow
Cheryl Hawkes, Department of Biomedical and Life Sciences, Lancaster University
Summary:
Neurons are highly energy-demanding cells that require a constant supply of glucose—the fuel behind all brain functions, including learning, memory, and cognition. Glial cells, such as astrocytes and oligodendrocytes, provide energy-rich metabolites to active neurons, limit inflammation, and support cognition. However, how neurons communicate their energy needs to glial cells, and how glia metabolically respond, remains poorly understood.
Our recent work suggests that adenosine molecules, released during increased neuronal activity, act as metabolic signals to activate astrocyte glucose metabolism, supporting key brain functions such as learning, memory, and sleep. This project will investigate the molecular mechanisms by which astrocytes and oligodendrocytes regulate glucose uptake and metabolism to sustain neuronal activity and brain function.
Ageing is associated with a progressive decline in brain energy metabolism, or hypometabolism, which contributes to neuroinflammation, neurodegeneration, and cognitive impairment. The molecular mechanisms underlying this energetic decline remain unclear. This project will explore whether glial metabolic regulation changes in the ageing brain, offering insights into age-related inflammation, neurodegeneration, and cognitive decline, with potential translational relevance.
The student will gain training in advanced live-cell fluorescence imaging to monitor intracellular Ca²⁺, cAMP dynamics, and key energy metabolites such as glucose, NADH, and ATP. They will also perform biochemical and molecular analyses of adenosine receptor expression in the glial-vascular unit and conduct animal behavioural studies.