title: Branched-chain amino acids influence the immune properties of microglial cells and their responsiveness to pro-inflammatory signals.
abstract: The branched-chain amino acids (BCAAs) valine, leucine and isoleucine are essential amino acids involved in several important brain functions. Although commonly used as nutritional supplements, excessive intake of BCAAs might favour the establishment of neurotoxic conditions as indicated by the severe neurological symptoms characterising inherited disorders of BCAA catabolism such as maple syrup urine disease (MSUD). Recent evidence indicates that BCAAs induce excitotoxicity through mechanisms that require the presence of astrocytes. In the present study, we evaluated the effects of BCAAs on microglia, the main immune cells of the brain. As an experimental model we used primary microglial cells harvested from mixed glial cultures that had been kept in normal or high BCAA medium (H-BCAA). We show that H-BCAA microglial cells exhibit a peculiar phenotype characterized by a partial skewing toward the M2 state, with enhanced IL-10 expression and phagocytic activity but also increased free radical generation and decreased neuroprotective functions. We suggest that such an intermediate M1/M2 phenotype might result in a less efficient microglial response, which would promote the establishment of a low grade chronic inflammation and increase the likelihood of neurodegeneration. Although based on in vitro evidence, our study adds on to an increasing literature indicating that the increasing use of dietary integrators might deserve consideration for the possible drawbacks. In addition to excitotoxicity, the altered immune profile of microglia might represent a further mechanism by which BCAAs might turn into toxicants and facilitate neurodegeneration.
authors: Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy.
authors: Roberta
authors: R
authors: De Simone
authors: Federica
authors: F
authors: Vissicchio
authors: Cecilia
authors: C
authors: Mingarelli
authors: Chiara
authors: C
authors: De Nuccio
authors: Sergio
authors: S
authors: Visentin
authors: Maria Antonietta
authors: MA
authors: Ajmone-Cat
authors: Luisa
authors: L
authors: Minghetti
mesh_terms: D000597:Amino Acids, Branched-Chain / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D005609:Free Radicals / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000494:pharmacology; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D017628:Microglia / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects*; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020123:Sirolimus / Q000494:pharmacology
chemical_list: D000597:Amino Acids, Branched-Chain; D016207:Cytokines; D005609:Free Radicals; D007166:Immunosuppressive Agents; D008070:Lipopolysaccharides; D016753:Interleukin-10; D020123:Sirolimus