Biochemical and Biophysical Research Communications
Galantamine modulates nicotinic receptor and blocks Aβ-enhanced glutamate toxicity
Section snippets
Materials and methods
Experiments were carried out on animals treated in accordance with the guidelines published in the National Institutes of Health Guide for the Care and Use of Laboratory Animals.
Materials. The sources of drugs and materials were as follows: Eagle’s minimum essential medium (EMEM) (Nissui Pharmaceutical, Tokyo, Japan); (−)-nicotine, MK801, methyllycaconitine (MLA), and mecamylamine (Sigma-RBI, Natick, MA); α-bungarotoxin (αBTX) (Wako Pure Chemical Industries, Osaka, Japan); galantamine HBr, PI3K
Galantamine protects neurons from Aβ-enhanced glutamate cytotoxicity
Cortical neurons were incubated with both Aβ1–40 (10 nM) and Aβ1–42 (1.0 nM) for 4 days, which did not directly induce cell death. Treatment with a low dose (20.0 μM) of glutamate alone did not significantly induce cell death (Figs. 1A and B), but exposure to the same dose of glutamate for 24 h (20.0 μM) caused a significant reduction in the number of Aβ-treated neuronal cells (Figs. 1A and B). Co-incubating the cultures with galantamine and Aβ significantly reduced Aβ-enhanced glutamate
Discussion
Galantamine allosterically modulates both α7 and α4β2 nAChRs [9], [19], besides its activity as an AChEI [1] which could increase ACh levels via the inhibition of AChE. And both α7 and α4β2 nAChR stimulation protect neurons from Aβ- and glutamate-induced neuronal death [6], [7], [8], [14]. Therefore, it is possible that galantamine exerts a neuroprotective effect.
Aβ accumulation is one of the earliest changes in AD pathology, and this peptide may cause neuronal death in the central nervous
Acknowledgments
This study was supported in part by Grants-in-Aid for scientific research from the Ministry of Education, Culture, Sports, Science and Technology of Japan, and by grants from the Ministry of Health, Labour and Welfare of Japan, and the Smoking Research Foundation.
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