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Title

Neuroprotection afforded by nicotine against oxygen and glucose deprivation in hippocampal slices is lost in α7 nicotinic receptor knockout mice

AuthorsSobrado, Mónica ; López, Manuela G.; García, A. G.
Issue Date2007
PublisherElsevier
CitationNeuroscience 145(3): 866-872 (2007)
AbstractAlthough α7-receptors are considered the main target for neuroprotection, other receptor subtypes (α4β2 or α3β4) have also been implicated. Hence, we have used α7-transgenic mice, to study the hypothesis that α7-receptors play a dominant role in mediating neuroprotection in an in vitro model of ischemia. We have used rat and mouse hippocampal slices to establish the model of nicotinic neuroprotection against oxygen and glucose deprivation (OGD). Neuronal damage caused by OGD during 1 h plus 3 h re-oxygenation, was quantified by measuring lactate dehydrogenase (LDH) release from hippocampal slices. In rat hippocampal slices, OGD increased over twofold basal LDH release. Such increase was reduced when treated with 10-100 μM nicotine; maximal protection afforded by nicotine amounted to 46%. This neuroprotection was antagonized by the non-selective nicotinic receptor for acetylcholine (nAChR) blocker mecamylamine (10 μM). In hippocampal slices from wild-type control mice, nicotine (100 μM) decreased by 54.4% LDH release evoked by OGD plus re-oxygenation. In contrast, nicotine failed to exert neuroprotection in α7 knockout mice. This finding reinforces the view that the hippocampal neuroprotective effects of nicotine are predominantly linked to α7 receptors. © 2007 IBRO.
URIhttp://hdl.handle.net/10261/81786
DOI10.1016/j.neuroscience.2006.12.036
Identifiersdoi: 10.1016/j.neuroscience.2006.12.036
issn: 0306-4522
e-issn: 1873-7544
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