A team led by Rosa Chiara Paolicelli, from the Department of Biomedical Sciences at the University of Lausanne, describes how lactate promotes lysosome function in microglia, while having various consequences on other brain cells, such as neurons.
Microglia are small glial cells scattered throughout the central nervous system (brain, spinal cord and retina). These cells act as phagocytes and are capable of engulfing and destroying pathogenic foreign agents, thus constituting the main immune defense of the central nervous system. Research on microglia has evolved considerably over the last decade, revealing new and previously unsuspected functions of this cell population in brain physiology and pathology.
Lactate is a particularly abundant metabolite in the brain, but its use by microglia has been little studied until now. Microglia perform their phagocytic function with the help of their lysosomes, the organelles in their cytoplasm responsible for intracellular degradation.
Microglia and neuropathologies
The authors of the article just published in Nature Communications show that altering lactate transport in mouse brain microglia results in defective brain development, with increased vulnerability to epileptic seizures in particular. Overall, these results demonstrate that selective disruption of the MCT4 monocarboxylate transporter in microglia prevents lactate-induced lysosomal modulation. This deregulation is sufficient to alter synapses and induce defects in neural function in mice. This affects their behavior in adulthood, increasing their anxiety levels and innate fear’, explains Katia Monsorno , first author of the study and researcher at the Microglia Biology Laboratory, part of the Department of Biomedical Sciences at the Faculty of Biology and Medicine, University of Lausanne.
Given the established role of microglia in neuropathologies, an understanding of the mechanism of microglial modulation by lactate could prove relevant for targeting this in different brain diseases.