Dietary carnosine intake improves outcomes in Experimental Autoimmune Encephalomyelitis

Background: Carnosine (C9H14N4O3) is a naturally occurring dipeptide synthetized from histidine and β-alanine that is mainly found in excitable tissues such as skeletal muscle and the central nervous system (CNS). Here, carnosine serves versatile functions to protect the CNS and preserve homeostasis (e.g. antioxidant, antiglycation, reactive aldehyde quenching). We investigated the effect of carnosine treatment in Experimental Autoimmune Encephalomyelitis (EAE), an animal model for neuroinflammation and demyelination that mimics multiple sclerosis (MS). Methods: To induce EAE, female C57/BL6 mice were actively immunized with MOG35-55 followed by i.p. injection with pertussis toxin. Mice receiving carnosine (0.3%, 1.5%, or 3%) in their drinking water were compared with mice receiving normal tap water. All mice were sacrificed 56 days post immunization. Results: Dietary carnosine intake (3%) reduced clinical EAE severity compared to controls, 0.3% carnosine and 1.5% carnosine. Immunohistochemistry revealed a reduced number of T lymphocytes (CD3+ ) and microglia/macrophages (F4/80+ ) in the spinal cord. TNF-α mRNA abundance decreased and brain-derived neurotrophic factor (BDNF) increased in animals treated with 3% carnosine. Conclusion: Carnosine treatment effectively reduced clinical EAE severity, which was paralleled by changes in bio- and histochemical analyses. Future research is warranted to unravel the underlying mechanisms of carnosine treatment for neuroinflammatory and demyelinating disorders.