The subpopulation of microglia expressing functional muscarinic acetylcholine receptors expands in stroke and Alzheimer’s disease

• Published in: Brain Structure and Function Vol. 221; no. 2; pp. 1157 - 1172
• Main Authors: Pannell, Maria, Meier, Maria Almut, Szulzewsky, Frank, Matyash, Vitali, Endres, Matthias, Kronenberg, Golo, Prinz, Vincent, Waiczies, Sonia, Wolf, Susanne A., Kettenmann, Helmut
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.03.2016; Springer Nature B.V
• Subjects: Alzheimer Disease - metabolism; Alzheimer's disease; Animals; Biomedical and Life Sciences; Biomedicine; Brain; Brain - metabolism; Carbachol - pharmacology; Cell Biology; Disease Models, Animal; Female; Glioma - metabolism; Macrophages - drug effects; Macrophages - metabolism; Male; Mice; Microglia - metabolism; Models, Animal; Multiple Sclerosis - metabolism; Muscarinic Agonists - pharmacology; Neurobiology; Neurology; Neurosciences; Neurotransmitter Agents - metabolism; Original Article; Receptor, Muscarinic M2 - metabolism; Receptor, Muscarinic M3 - metabolism; Receptors, Muscarinic - biosynthesis; Stroke; Stroke - metabolism; Stroke; Multiple sclerosis; Alzheimer’s disease; Glioma; Brain macrophages; Muscarinic acetylcholine receptors; Microglia
• ISSN: 1863-2653; 1863-2661; 0340-2061
• DOI: 10.1007/s00429-014-0962-y

Microglia undergo a process of activation in pathology which is controlled by many factors including neurotransmitters. We found that a subpopulation (11 %) of freshly isolated adult microglia respond to the muscarinic acetylcholine receptor agonist carbachol with a Ca 2+ increase and a subpopulation of similar size (16 %) was observed by FACS analysis using an antibody against the M3 receptor subtype. The carbachol-sensitive population increased in microglia/brain macrophages isolated from tissue of mouse models for stroke (60 %) and Alzheimer’s disease (25 %), but not for glioma and multiple sclerosis. Microglia cultured from adult and neonatal brain contained a carbachol-sensitive subpopulation (8 and 9 %), which was increased by treatment with interferon-γ to around 60 %. This increase was sensitive to blockers of protein synthesis and correlated with an upregulation of the M3 receptor subtype and with an increased expression of MHC-I and MHC-II. Carbachol was a chemoattractant for microglia and decreased their phagocytic activity.