Nicotinic α7 receptors protect against glutamate neurotoxicity and neuronal ischemic damage

doi:10.1016/S0006-8993(97)00194-7

Brain Research

Volume 779, Issues 1–2, 1 January 1998, Pages 359-363

https://doi.org/10.1016/S0006-8993(97)00194-7 Get rights and content

Abstract

The α7 receptor agonist dimethoxybenzylidene anabaseine (DMXB) protected rat neocortical neurons against excitotoxicity administered 24 h before, but not concomitantly with, NMDA. This action was blocked by nicotinic but not muscarinic antagonists. DMXB (1 mg/kg i.p.) also reduced infarct size in rats when injected 24 h before, but not during, focal ischemic insults. In a mecamylamine-sensitive manner, α7 receptors appear neuroprotective in non-apoptotic model.

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Acknowledgements

This study was supported in part of NIH P01AG10485, Grants-in-Aid for Scientific Research from the Ministry of Education, Science, Sports, and Culture of Japan, grants from the Ministry of Welfare of Japan, and the Smoking Research Foundation. We also thank Taiho Pharmaceutical Co. for providing DMXB and Craig Meyers for technical assistance.

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In this review we will focus on cholinergic, glutamatergic and nitrinergic transmission, because of their central role in learning and memory and their impairment in neurodegenerative disorders such as Alzheimer’s disease.
Pre-clinical studies performed on healthy adult animals and aged animals, as well as transgenic animal models of AD, have suggested a biphasic DR for acetylcholine, glutamate and nitric oxide. This stresses the relevance to perform DR curves when studying the mechanisms underlying synaptic plasticity and memory, the pharmacological profile of cognitive-enhancing drugs acting on these systems, and the possibility to combine low/ineffective doses of drugs that might have additive/synergistic effects, reducing the unwanted side effects associated to the high doses.
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Short communicationNicotinic α7 receptors protect against glutamate neurotoxicity and neuronal ischemic damage

Abstract

Section snippets

Acknowledgements

Trends Neurosci.

Neurosci. Lett.

Neuron

Neuron

Nicotine-induced protection of cultured cortical neurons against N-methyl-d-asparate receptor-mediated glutamate cytotoxicity

Brain Res.

Diversity of nicotinic acetylcholine receptors in rat hippocampal neurons II. The rundown and inward rectifications of agonist-elicited whole-cell currents and identification of receptor subunits by in situ hybridization

J. Phamacol. Exp. Ther.

Short communication
Nicotinic α7 receptors protect against glutamate neurotoxicity and neuronal ischemic damage