Title:Cholinergic System and Neuroinflammation: Implication in Multiple Sclerosis
Volume: 17
Issue: 2
Author(s): Maria Di Bari, Giovanni Di Pinto, Marcella Reale, Guadalupe Mengod*Ada Maria Tata*
Affiliation:
- IIBB-CSIC, IDIBAPS, CIBERNED, Rosselló 161, Barcelona 08036,Spain
- Dipartimento di Biologia e Biotecnologie Charles Darwin, Centro di ricerca in Neuroscienze Daniel Bovet, Sapienza, Università di Roma, P.le Aldo Moro, 5, 00185 Roma,Italy
Keywords:
Acetylcholine, cholinergic markers, inflammation, multiple sclerosis, muscarinic receptors, nicotinic receptors.
Abstract: Background: Multiple sclerosis (MS) is an inflammatory and neurodegenerative disease of
the central nervous system (CNS) characterized by leucocytes infiltration, demyelination, axonal degeneration
and neuronal death. Although the etiology of MS is still unkwon, inflammation and autoimmunity
are considered to be key players of the disease.
Nervous System: The severe alterations affecting the nervous system contribute to the motor and
cognitive disabilities and are in large part dependent on severe inflammatory processes active in both
central nervous system and immune system. Acetylcholine (ACh) appears to be involved in the
modulation of central and peripheral inflammation. Immune cells as well as astrocytes and microglia
respond to ACh stimuli by activation of cholinergic receptors. Muscarinic and nicotinic receptors differently
contribute to the modulation of immunological and inflammatory processes stimulating pro- and
anti-inflammatory cytokines respectively. The role played by ACh in MS is not yet fully understood,
although some results point to its involvement in different neurological disorders such as Alzheimer’s
disease and schizophrenia.
Conclusion: In the present review we summarize the evidence indicating the correlation between
nervous system dysfunction in MS, with inflammation and cholinergic system alterations. Experiments
performed in MS animal models and analyses on biological fluids from MS patients such as
blood, serum and cerebrospinal fluid suggest that cholinergic alterations may contribute to the dysregulated
inflammatory processes of MS. Many current therapeutic approaches in MS are based on
anti-inflammatory drugs. We also discuss how the use of cholinesterase inhibitors or ACh mimetics
may represent a new interesting therapeutic approach in MS.
