Comparative study of the expression of cholinergic system components in the CNS of experimental autoimmune encephalomyelitis mice: Acute vs remitting phase

Acetylcholine (ACh) is involved in the modulation of the inflammatory response. ACh levels are regulated by its synthesizing enzyme, choline acetyltransferase (ChAT), and by its hydrolyzing enzymes, mainly acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). A more comprehensive understanding of the cholinergic system in experimental autoimmune encephalomyelitis (EAE) disease progression could pave the path for the development of therapies to ameliorate multiple sclerosis (MS). In this work, we analyzed possible alterations of the CNS cholinergic system in the neuroinflammation process by using a MOG‐induced EAE mice model. MOG‐ and vehicle‐treated animals were studied at acute and remitting phases. We examined neuropathology and analyzed mRNA expression of ChAT, AChE and the α7 subunit of the nicotinic acetylcholine receptor (α7nAChR), as well as AChE and BuChE enzyme activities, in brain and spinal cord sections during disease progression. The mRNA expression and enzyme activities of these cholinergic markers were up‐ or down‐regulated in many cholinergic areas and other brain areas of EAE mice in the acute and remitting phases of the disease. BuChE was present in a higher proportion of astroglia and microglia/macrophage cells in the EAE remitting group. The observed changes in cholinergic markers expression and cellular localization in the CNS during EAE disease progression suggests their potential involvement in the development of the neuroinflammatory process and may lay the ground to consider cholinergic system components as putative anti‐inflammatory therapeutic targets for MS.
This work was supported by grants awarded by Fondazione Italiana Sclerosi Multipla (FISM 2013/R/25) to A.M.T, by Instituto de Salud Carlos III, PI-10/01874 and PI-15/00148, cofinanced by the European Regional Development Fund.,“Una manera de hacer Europa” and by the Generalitat de Catalunya (SGR2014/798) to G.M. GDP was supported by ERASMUS/ERASMUS+ project from Sapienza, University of Rome and by Torno Subito project from Regione Lazio, Italy. MDB was supported by FISM, and Ateneo Sapienza, University of Rome and the travel grant was supported by CIB (Consorzio Interuniversitario Biotecnologie). VG and SS were supported by FISM and University of Chieti-Pescara G. D’Annunzio.