Branched-chain amino acids influence the immune properties of microglial cells and their responsiveness to pro-inflammatory signals
- PMID: 23402925
- DOI: 10.1016/j.bbadis.2013.02.001
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.
Copyright © 2013 Elsevier B.V. All rights reserved.
Similar articles
-
Administration of branched-chain amino acids increases the susceptibility to lipopolysaccharide-induced inflammation in young Wistar rats.Int J Dev Neurosci. 2019 Nov;78:210-214. doi: 10.1016/j.ijdevneu.2019.07.007. Epub 2019 Jul 19. Int J Dev Neurosci. 2019. PMID: 31330240
-
L-carnitine Prevents Oxidative Stress in the Brains of Rats Subjected to a Chemically Induced Chronic Model of MSUD.Mol Neurobiol. 2016 Nov;53(9):6007-6017. doi: 10.1007/s12035-015-9500-z. Epub 2015 Nov 2. Mol Neurobiol. 2016. PMID: 26526843
-
Branched-chain amino acids accumulating in maple syrup urine disease induce morphological alterations in C6 glioma cells probably through reactive species.Int J Dev Neurosci. 2007 May;25(3):181-9. doi: 10.1016/j.ijdevneu.2007.01.001. Epub 2007 Jan 21. Int J Dev Neurosci. 2007. PMID: 17317075
-
Branched-chain amino acids as pharmacological nutrients in chronic liver disease.Hepatology. 2011 Sep 2;54(3):1063-70. doi: 10.1002/hep.24412. Epub 2011 Jun 23. Hepatology. 2011. PMID: 21563202 Review.
-
Neuronal injury in chronic CNS inflammation.Best Pract Res Clin Anaesthesiol. 2010 Dec;24(4):551-62. doi: 10.1016/j.bpa.2010.11.001. Epub 2010 Nov 29. Best Pract Res Clin Anaesthesiol. 2010. PMID: 21619866 Review.
Cited by
-
Changes in dietary habits and eating behaviors during COVID-19 induced confinement: A study from Jordan.Hum Nutr Metab. 2022 Dec;30:200169. doi: 10.1016/j.hnm.2022.200169. Epub 2022 Nov 13. Hum Nutr Metab. 2022. PMID: 38620861 Free PMC article.
-
Microbiota-gut-brain axis and its therapeutic applications in neurodegenerative diseases.Signal Transduct Target Ther. 2024 Feb 16;9(1):37. doi: 10.1038/s41392-024-01743-1. Signal Transduct Target Ther. 2024. PMID: 38360862 Free PMC article. Review.
-
Effects of Branched-Chain Amino Acids on the Inflammatory Response Induced by LPS in Caco-2 Cells.Metabolites. 2024 Jan 22;14(1):76. doi: 10.3390/metabo14010076. Metabolites. 2024. PMID: 38276311 Free PMC article.
-
Acute ischemia induces spatially and transcriptionally distinct microglial subclusters.Genome Med. 2023 Dec 11;15(1):109. doi: 10.1186/s13073-023-01257-5. Genome Med. 2023. PMID: 38082331 Free PMC article.
-
Maternal suboptimal selenium intake and low-level lead exposure affect offspring's microglial immune profile and its reactivity to a subsequent inflammatory hit.Sci Rep. 2023 Dec 5;13(1):21448. doi: 10.1038/s41598-023-45613-2. Sci Rep. 2023. PMID: 38052845 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Research Materials