RT Journal Article
T1 Galantamine elicits neuroprotection by inhibiting iNOS, NADPH oxidase and ROS in hippocampal slices stressed with anoxia/reoxygenation
A1 Egea, Javier
A1 Martín De Saavedra Álvarez De Uribarri, María Dolores
A1 Parada, Esther
A1 Romero Martínez, Manuel Alejandro
A1 Barrio, Laura del
A1 Rosa, Angelo Oscar
A1 García, Antonio
A1 López, Manuela
AB 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 mM, 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 NFkB/iNOS.
SN 0028-3908
YR 2011
FD 2011
LK https://hdl.handle.net/20.500.14352/93554
UL https://hdl.handle.net/20.500.14352/93554
LA eng
NO Egea J, Martín-de-Saavedra MD, Parada E, Romero A, Del Barrio L, Rosa AO, et al. Galantamine elicits neuroprotection by inhibiting iNOS, NADPH oxidase and ROS in hippocampal slices stressed with anoxia/reoxygenation. Neuropharmacology 2012;62:1082–90. https://doi.org/10.1016/j.neuropharm.2011.10.022
NO Instituto de Salud Carlos III (España)
NO Fundación Teófilo Hernando (España)
NO Ministerio de Ciencia e Innovación (España)
NO Comunidad de Madrid
DS Docta Complutense
RD 25 abr 2025