Possible Correlation between Cholinergic System Alterations and Neuro/Inflammation in Multiple Sclerosis
Multiple sclerosis (MS) is an autoimmune and demyelinating disease of the central
nervous system. Although the etiology of MS is still unknown, both genetic and environmental
factors contribute to the pathogenesis of the disease. Acetylcholine participates in the modulation
of central and peripheral inflammation. The cells of the immune system, as well as microglia,
astrocytes and oligodendrocytes express cholinergic markers and receptors of muscarinic and
nicotinic type. The role played by acetylcholine in MS has been recently investigated. In the present
review, we summarize the evidence indicating the cholinergic dysfunction in serum and
cerebrospinal fluid of relapsing–remitting (RR)‐MS patients and in the brains of the MS animal
model experimental autoimmune encephalomyelitis (EAE). The correlation between the increased
activity of the cholinergic hydrolyzing enzymes acetylcholinesterase and butyrylcholinesterase, the
reduced levels of acetylcholine and the increase of pro‐inflammatory cytokines production were
recently described in immune cells of MS patients. Moreover, the genetic polymorphisms for both
hydrolyzing enzymes and the possible correlation with the altered levels of their enzymatic activity
have been also reported. Finally, the changes in cholinergic markers expression in the central
nervous system of EAE mice in peak and chronic phases suggest the involvement of the
acetylcholine also in neuro‐inflammatory processes.