Glial Glycolysis Is Essential for Neuronal Survival in Drosophila

Abstract

Neuronal information processing requires a large amount of energy, indicating that sugars and other metabolites must be efficiently delivered. However, reliable neuronal function also depends on the maintenance of a constant microenvironment in the brain. Therefore, neurons are efficiently separated from circulation by the blood-brain barrier, and their long axons are insulated by glial processes. At the example of the Drosophila brain, we addressed how sugar is shuttled across the barrier to nurture neurons. We show that glial cells of the blood-brain barrier specifically take up sugars and that their metabolism relies on glycolysis, which, surprisingly, is dispensable in neurons. Glial cells secrete alanine and lactate to fuel neuronal mitochondria, and lack of glial glycolysis specifically in the adult brain causes neurodegeneration. Our work implies that a global metabolic compartmentalization and coupling of neurons and glial cells is a conserved, fundamental feature of bilaterian nervous systems independent of their size.

A novel ex vivo method for measuring whole brain metabolism in model systems

“…While lactate production can be measured in Drosophila cultured cells, and increases are detected upon mitochondrial challenge or gene mutation (Freije, Mandal, & Banerjee, 2012), it is less clear whether lactate produced by glial cells would enter the extracellular environment and be detected in the media. As reported in Volkenhoff et al ., glial cells are able to produce lactate, but this lactate is then utilized by neurons (Volkenhoff et al, 2015). From this analysis we were able to detect decreases in PER reflecting decreased lactate levels and media acidification in wild type brains, but not LDH deficient brains.…”

Redirecting N-acetylaspartate metabolism in the central nervous system normalizes myelination and rescues Canavan disease

“…This theory implies that either a compensating mechanism for oligodendroglial NAA exists as inferred from the work of others (41,42) or the function of NAA can be rerouted to astrocytes to provide essential metabolites to oligodendrocytes (43). Given the metabolic connections among glial cells, it would not be surprising if metabolic support is not only provided from glia to neurons but also among glial cells, potentially establishing the NAA metabolism in astrocytes to provide aspartate and acetate to oligodendrocytes (44). In that context, the efficacy of our 3rd generation hASPA expression system highlights its general usefulness for the study of NAA metabolism in different cells and tissues.…”

Glial contributions to neuronal health and disease: new insights from Drosophila

“…Volkenhoff and colleagues (2015) now show that Drosophila employ a “glia to neuron” shuttling system to provide these critical metabolic factors to neurons. The perineurial glial cells of the blood brain barrier specifically express the trehalose transporter Tret1-1 to absorb trehalose from the hemolymph (19). Within this subset of glia, trehalose is first broken down to glucose and then further metabolized to alanine or lactate, which can be taken up by local neurons to meet energy demands.…”