@article{oai:showa.repo.nii.ac.jp:00001163, author = {ITOH, Yoshitsugu and TANAKA, Sachiko and TAKAHASHI, Sayaka and MORIKWA, Chikara and NUMAZAWA, Satoshi and KAIZAKI, Asuka and YOSHIDA, Takemi}, issue = {1}, journal = {昭和大学薬学雑誌}, month = {2011-06, 2019-07-26}, note = {Nicotine, main constituent of tabaco, is known as a nicotinic acetylcholine receptor (nAChR) agonist and increases cognitive performance. 3-(2,4-dimethoxybenzylidene)-anabaseine (GTS-21) is derived from the marine worm toxin, anabaseine, and is alpha7-selective nAChR (D7-nAChR) agonist. Both nicotine and GTS-21 were expected as therapeutic agents of Alzheimer’s disease. Several studies showed that nicotine and GTS-21 protected neuron by activating nAChR, especially D7-nAChR. It has been reported that D7-nAChR has been shown to be an essential regulator of inflammation. The purpose of this study is to examine the neuroprotective and anti-inflammatory effects of nicotine and GTS-21 using organotypic hippocampal slice cultures. Kainic acid (KA, 5-50µM) induced concentration- and time-dependent neuronal cell death in the hippocampal organotypic slice cultures. The pretreatment with nicotine and GTS-21 tended to decrease in KA toxicity. In a CA3 area-specific analysis, pretreatment with nicotine resulted in significant inhibition of KA-induced neurotoxicity. The results suggest that nicotine may protect KA-induced neuronal cell death via D7-nAChR. We also examined anti-inflammatory effects of nicotine and GTS-21. Hippocampal slices were pretreated with nicotine or GTS-21, and then treated with lipopolysaccharide (LPS). LPS treatment induced concentration-dependent increases in TNFD and IL-1E gene expressions. LPS-induced TNFD gene expression, but not IL-1E was suppressed by GTS-21 pretreatment. These results suggest that D7-nAChR might be involved in the microglia activation towards a neuroprotective role by suppressing inflammatory cytokine.}, pages = {71--81}, title = {Alpha7 nicotinic ACh receptor mediated neuroprotective action by nicotine and GTS-21: An approach by the hippocampal organotypic slice cultures.}, volume = {2}, year = {} }