Astrocytes are the stars in the ageing brain
The effects of ageing on brain function can seriously affect otherwise healthy individuals. In the ageing brain, most research has focused on the neurons while the importance of astrocytes, the most numerous cell type in brain, have been largely ignored. The knowledge on the multitude of functions performed by astrocytes is constantly increasing, but details of how ageing can affect astrocyte energy metabolism remain incomplete. Funded by the EU, the ASTROAGE (Astrocytes in aging brain exhibit altered glutamate homeostasis: Implications for age related cognitive decline?) project looked at the consequences of ageing on astrocytes. The researchers compared the metabolic activity in astrocytes in the hippocampus of young mice at 4 and 22 months old. Using 13-C labelled energy substrates such as glutamate, glucose and acetate they investigated age-related effects on neuronal and astrocytic metabolism, with special emphasis on glutamate since it is primarily taken up by astrocytes and can be a valuable source of energy under low-glucose conditions. Project results showed that the metabolic properties of the older mouse astrocytes are geared towards more efficient use of glutamate for energy production. Glycogen storage also increases in the old brain which may be an indication of altered glucose metabolism. Moreover, intermediates in the tricarboxylic acid (TCA) cycle, fumarate and citrate, are also differentially regulated in the ageing brain, which could indicate an imbalance in reactions in the cycle. Researchers also investigated changes in levels of glutamate dehydrogenase (GDH), an enzyme that converts glutamate to alpha-ketoglutarate, an intermediate in the TCA cycle. Indeed, results showed that hippocampal slices exhibit a very high level of GDH activity, but no age-related differences could be proven. Overall findings indicate a very close connection between glutamate input to the TCA cycle through GDH activity and glucose metabolism. As any disturbance in energy production homeostasis may lead to neurodegeneration, a thorough understanding of the contribution of astrocytes to brain ageing processes is crucial to counteract cognitive decline in older people. ASTROAGE has laid a firm knowledge foundation for more in-depth studies particularly relevant in an ageing Europe.