Using stable isotope tracing to unravel the metabolic components of neurodegeneration: Focus on neuron-glia metabolic interactions

Disrupted brain metabolism is a critical component of several neurodegenerative diseases. Energy metabolism of both neurons and astrocytes is closely connected to neurotransmitter recycling via the glutamate/GABAglutamine cycle. Neurons and astrocytes hereby work in close metabolic collaboration which is essential to sustain neurotransmission. Elucidating the mechanistic involvement of altered brain metabolism in disease progression has been aided by the advance of techniques to monitor cellular metabolism, in particular by mapping metabolism of substrates containing stable isotopes, a technique known as isotope tracing. Here we review key aspects of isotope tracing including advantages, drawbacks and applications to different cerebral preparations. In addition, we narrate how isotope tracing has facilitated the discovery of central metabolic features in neurodegeneration with a focus on the metabolic cooperation between neurons and astrocytes.

Automated summary

Disrupted brain metabolism is crucial for neurodegenerative diseases, and the energy metabolism of neurons and astrocytes through the glutamate/GABA-glutamine cycle plays a vital role in neurotransmitter recycling. Isotope tracing, a technique to monitor cellular metabolism, has helped elucidate the mechanistic involvement of altered brain metabolism in disease progression. This review discusses the advantages, drawbacks, and applications of isotope tracing in different cerebral preparations and narrates how it has facilitated the discovery of central metabolic features in neurodegeneration, particularly in the metabolic cooperation between neurons and astrocytes.