title: The Cholinergic Signaling Responsible for the Expression of a Memory-Related Protein in Primary Rat Cortical Neurons.
abstract: Cholinergic dysfunction in the brain is closely related to cognitive impairment including memory loss. In addition to the degeneration of basal forebrain cholinergic neurons, deficits in the cholinergic receptor signaling may also play an important role. In the present study, to examine the cholinergic signaling pathways responsible for the induction of a memory-related postsynaptic protein, a cholinergic agonist carbachol was used to induce the expression of activity-regulated cytoskeleton associated protein (Arc) in primary rat cortical neurons. After pretreating neurons with various antagonists or inhibitors, the levels of carbachol-induced Arc protein expression were detected by Western blot analysis. The results show that carbachol induces Arc protein expression mainly through activating M1 acetylcholine receptors and the downstream phospholipase C pathway, which may lead to the activation of the MAPK/ERK signaling pathway. Importantly, carbachol-mediated M2 receptor activation exerts negative effects on Arc protein expression and thus counteracts the enhanced effects of M1 activation. Furthermore, it is suggested for the first time that M1-mediated enhancement of N-methyl-D-aspartate receptor (NMDAR) responses, leading to Ca(2+) entry through NMDARs, contributes to carbachol-induced Arc protein expression. These findings reveal a more complete cholinergic signaling that is responsible for carbachol-induced Arc protein expression, and thus provide more information for developing treatments that can modulate cholinergic signaling and consequently alleviate cognitive impairment. J. Cell. Physiol. 231: 2428-2438, 2016. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Physiology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Tsan-Ju
authors.initials: TJ
authors.lastname: Chen
authors.affiliation: Department of Neurology, Chang Gung Memorial Hospital, Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Shun-Sheng
authors.initials: SS
authors.lastname: Chen
authors.affiliation: Department of Sports Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Dean-Chuan
authors.initials: DC
authors.lastname: Wang
authors.affiliation: Department of Physiology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Hui-Shan
authors.initials: HS
authors.lastname: Hung
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology*; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D008568:Memory / Q000187:drug effects; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D043643:Receptor, Muscarinic M1 / Q000037:antagonists & inhibitors; D043585:Receptor, Muscarinic M2 / Q000037:antagonists & inhibitors; D011950:Receptors, Cholinergic; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D010738:Type C Phospholipases / Q000378:metabolism; D019061:src-Family Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D003598:Cytoskeletal Proteins; D009419:Nerve Tissue Proteins; D043643:Receptor, Muscarinic M1; D043585:Receptor, Muscarinic M2; D011950:Receptors, Cholinergic; D016194:Receptors, N-Methyl-D-Aspartate; C092069:activity regulated cytoskeletal-associated protein; D002217:Carbachol; D019061:src-Family Kinases; D010738:Type C Phospholipases; D000109:Acetylcholine; D002118:Calcium