title: Galantamine elicits neuroprotection by inhibiting iNOS, NADPH oxidase and ROS in hippocampal slices stressed with anoxia/reoxygenation.
abstract: Galantamine is a drug currently used to treat Alzheimer's disease (AD); in this group of patients it has been observed that concomitant ischemic brain injury can accelerate their cognitive deficit. We have previously shown that galantamine can afford neuroprotection on in vitro and in vivo models related to brain ischemia. In this context, this study was planned to investigate the intracellular signaling pathways implicated in the protective effect of galantamine on an in vitro brain ischemia-reperfusion model, namely rat hippocampal slices subjected to oxygen and glucose deprivation (OGD) followed by reoxygenation. Galantamine protected hippocampal slices subjected to OGD in a concentration-dependent manner; at 15 μM, cell death was reduced to almost control levels. The neuroprotective effects of galantamine were reverted by mecamylamine and AG490, but not by atropine, indicating that nicotinic receptors and Jak2 participated in this action. Galantamine also prevented p65 translocation into the nucleus induced by OGD; this effect was also linked to nicotinic receptors and Jak2. Furthermore, galantamine reduced iNOS induction and production of NO caused by OGD via Jak2. ROS production by NADPH oxidase (NOX) activation was also inhibited by galantamine. In conclusion, galantamine afforded neuroprotection under OGD-reoxygenation conditions by activating a signaling pathway that involves nicotinic receptors, Jak2 and the consequent inhibition of NOX and NFκB/iNOS. This article is part of a Special Issue entitled 'Post-Traumatic Stress Disorder'.
authors.affiliation: Instituto Teófilo Hernando, Universidad Autónoma de Madrid, Spain. javier.egea@uam.es
authors.forename: J
authors.initials: J
authors.lastname: Egea
authors.forename: M D
authors.initials: MD
authors.lastname: Martín-de-Saavedra
authors.forename: E
authors.initials: E
authors.lastname: Parada
authors.forename: A
authors.initials: A
authors.lastname: Romero
authors.forename: L
authors.initials: L
authors.lastname: Del Barrio
authors.forename: A O
authors.initials: AO
authors.lastname: Rosa
authors.forename: A G
authors.initials: AG
authors.lastname: García
authors.forename: M G
authors.initials: MG
authors.lastname: López
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005702:Galantamine / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D000860:Hypoxia / Q000378:metabolism*; D053614:Janus Kinase 2 / Q000378:metabolism; D008297:Male; D019255:NADPH Oxidases / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*; D011978:Receptors, Nicotinic / Q000378:metabolism
chemical_list: D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D011978:Receptors, Nicotinic; D005702:Galantamine; D052247:Nitric Oxide Synthase Type II; D019255:NADPH Oxidases; D053614:Janus Kinase 2