Possible Correlation between Cholinergic System Alterations and Neuro/Inflammation in Multiple Sclerosis

Abstract

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.

Cardiac Autonomic Dysfunction in Myasthenia Gravis and Relapsing-Remitting Multiple Sclerosis—A Pilot Study

“…The VN stimulation suppress inflammation via cholinergic anti-inflammatory pathway. The cholinergic system has been suggested as a mediator between the nervus and immune systems and as a modulator of immune responses [ 20 , 21 ]. Thus, VN modulation may alleviate autoimmune disorders including MG and MS through acetylcholine release.…”

“…Pharmacological/electrical stimulation of VN leads to the release of acetylcholine which suppresses the production of TNF-α and other pro-inflammatory cytokines in lipopolysaccharide-stimulated human macrophage cultures [ 19 , 20 , 21 ]. Therefore, the modulation of vagal activity may result in beneficial therapeutic effects for both MG and MS patients [ 20 , 21 ]. Conversely, the cholinergic deficit observed in MG may contribute to the intensification of the autoimmune response.…”

Cholinergic Modulation of the Immune System in Neuroinflammatory Diseases

“…In MS patients, the expression of transcript for OCTN-1 and mediatophore, the two proteins typically expressed in immune cells and responsible for the non-vesicular ACh release, were also up-regulated, other than the ACh biosynthetic enzyme ChAT [ 79 , 80 ]. The dysregulated balance between ACh, AChE, and BChE could be responsible for higher pro-inflammatory cytokines production detected in MS patients [ 81 ].…”

The Combination of the M2 Muscarinic Receptor Agonist and Chemotherapy Affects Drug Resistance in Neuroblastoma Cells

“…Studies conducted in our laboratory have demonstrated that muscarinic receptors play relevant roles both in physiological and pathological conditions [ 16 , 17 , 18 , 19 , 20 , 21 ]. In recent years, the implication of muscarinic receptors has been largely reported as novel therapeutic targets for the treatment of different forms of cancers [ 22 ].…”