bioRxiv preprint doi: https://doi.org/10.1101/2021.01.18.427123; this version posted January 19, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY 4.0 International license. Cholinergic signalling in the forebrain controls microglial phenotype and responses to systemic inflammation Arshed Nazmi, Eadaoin W. Griffin, Robert H. Field, Sean Doyle1, Edel Hennessy, Martin O’Donnell, Aisling Rehill, Anthony McCarthy, Daire Healy, Michelle M. Doran1, John P. Lowry1, Colm Cunningham School of Biochemistry & Immunology, Trinity Biomedical Sciences Institute & Trinity College Institute of Neuroscience, Trinity College Dublin. 1Department of Chemistry, Maynooth University, Maynooth, Co. Kildare, Rep. of Ireland. Address for correspondence Colm Cunningham
[email protected] +353 1 896 3964 Keywords Acetylcholine, microglia, priming, delirium, sepsis, neuroinflammation, bioRxiv preprint doi: https://doi.org/10.1101/2021.01.18.427123; this version posted January 19, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY 4.0 International license. Abstract (250) Loss of basal forebrain cholinergic projections occurs in Alzheimer’s disease, frontotemporal dementia and in aging. Moreover, nicotinic stimulation is anti- inflammatory in macrophages and microglia but how loss of basal forebrain acetylcholine impacts on microglial phenotype is poorly understood. Here we hypothesized that endogenous ACh maintains homeostatic microglial phenotype and that neurodegeneration-evoked loss of ACh tone, triggers microglial activation.