Electronic Poster | Session 1

004 – Rapid plasticity of microglial metabolism sustains immune surveillance of the brain parenchyma.

Louis-Philippe Bernier (1*) – Elisa York (1*) – Alireza Kamyabi (1) – Hyun Beom Choi (1) – Brian MacVicar (1)
University of British Columbia, Djavad Mowafaghian Centre for Brain Health, Vancouver, Canada (1)

Microglia are highly motile cells that play a pivotal role in monitoring brain homeostasis by constantly probing the environment and responding to damage-associated cues. While it is generally believed that glucose is the main energy substrate used by brain cells, the specific energy requirements for microglial surveillance of the parenchyma remain unexplored. Here we show that microglia have a unique cellular metabolic signature and are capable of rapidly adapting their energy usage to substrates available in their environment. Using fluorescence lifetime imaging (FLIM) of intracellular NAD(P)H and time lapse 2-photon imaging of microglial dynamics in vivo and in situ as well as biochemical and cell culture approaches, we demonstrate that microglia can function using glutaminolysis as an alternative metabolic pathway. During insulin-induced hypoglycemia in vivo or in the absence of glucose in acute brain slices, microglial process motility and damage-sensing functions are unaltered. Pharmacological analysis reveals that glutamine is used by microglia under both normoglycemic and aglycemic conditions. The unique metabolic requirements of microglia were confirmed by measuring adaptive changes in intracellular NAD(P)H upon glucose removal. The metabolic activity of cultured microglia also reflected glutamine utilization when oxygen consumption rate, MTT oxydoreduction, and phagocytic activity were assayed. We further show that this rapid adaptation to metabolic sources is regulated by mTOR-dependent signalling. The remarkable metabolic plasticity suggests that microglia conserve their ability to react to environmental cues during metabolic challenges in the brain, even after neuroenergetic homeostasis is lost.