Investigating the mechanisms of neuron-glia signalling controlling brain energetics in healthy and ageing brains
Supervisors:
Dr Shefeeq Theparambil, Biomedical and Life Sciences, (Lancaster University)
Prof Julia Edgar, School of Infection and Immunity (University of Glasgow)
Dr Cheryl Hawkes, Faculty of Health and Medicine, (Lancaster University
Dr Neil Dawson, Faculty of Health and Medicine, (Lancater University)
Summary:
The brain requires a continuous supply of glucose, an essential nutrient, and oxygen to maintain optimal energy production because neurons consume significant amounts of energy for their critical functions, including learning, memory formation, and cognition.
Recent evidence highlights the crucial role of non-neuronal glial cells, especially astrocytes and oligodendrocytes, in supplying energy-rich molecules to meet neuronal energy needs during increased demand. However, the mechanisms by which neurons communicate their energy needs to glial cells and the molecular processes through which glial cells metabolically respond to support neurons are not yet fully understood. Our work suggests that adenosine molecules, released during increased neuronal activity, activate astrocyte glucose metabolism as a metabolic signal, supporting essential brain functions, including learning, memory, and sleep.
The student will investigate how astrocytes regulate glucose metabolism via adenosine-mediated signalling and whether similar mechanisms function in other glial cells, such as oligodendrocytes, to support neuronal energy production and essential brain functions. Ageing is marked by a significant reduction in brain energy metabolism (hypometabolism), which is linked to cognitive decline. This project will also explore whether neuron-glia metabolic signalling is altered in the ageing brain, potentially offering insight into age-related cognitive decline. The student will be trained in advanced live-cell fluorescence imaging techniques to measure intracellular Ca2+ and cAMP dynamics and monitor key energy metabolites such as glucose, NADH, and ATP. The student will also conduct biochemical and molecular analyses to evaluate adenosine receptor expression in the glial-vascular unit and engage in animal behavioural studies.
This project is a collaboration between Lancaster University (Dr Shefeeq Theparambil, Dr Cheryl Hawkes, and Dr Neil Dawson) and the University of Glasgow (Prof. Julia Edgar). The student will receive comprehensive training opportunities through these collaborations, including additional training at UCL through collaboration with Prof. Alexander Gourine's lab on optical imaging techniques and in vivo viral targeting of glial cells.