{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T02:23:02Z","timestamp":1789438982684,"version":"build-2803163510"},"reference-count":33,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2012,5,24]],"date-time":"2012-05-24T00:00:00Z","timestamp":1337817600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/2.0"},{"start":{"date-parts":[[2012,5,24]],"date-time":"2012-05-24T00:00:00Z","timestamp":1337817600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/2.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Neuroinflammation"],"published-print":{"date-parts":[[2012,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>Although evidence suggests that the prevalence of Parkinson\u2019s disease (PD) is lower in smokers than in non-smokers, the mechanisms of nicotine-induced neuroprotection remain unclear. Stimulation of the \u03b17 nicotinic acetylcholine receptor (\u03b17-nAChR) seems to be a crucial mechanism underlying the anti-inflammatory potential of cholinergic agonists in immune cells, including astrocytes, and inhibition of astrocyte activation has been proposed as a novel strategy for the treatment of neurodegenerative disorders such as PD. The objective of the present study was to determine whether nicotine-induced neuroprotection in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model occurs via \u03b17-nAChR-mediated inhibition of astrocytes.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>Both <jats:italic>in vivo<\/jats:italic> (MPTP) and <jats:italic>in vitro<\/jats:italic> (1-methyl-4-phenylpyridinium ion (MPP<jats:sup>+<\/jats:sup>) and lipopolysaccharide (LPS)) models of PD were used to investigate the role(s) of and possible mechanism(s) by which \u03b17-nAChRs protect against dopaminergic neuron loss. Multiple experimental approaches, including behavioral tests, immunochemistry, and stereology experiments, astrocyte cell cultures, reverse transcriptase PCR, laser scanning confocal microscopy, tumor necrosis factor (TNF)-\u03b1 assays, and western blotting, were used to elucidate the mechanisms of the \u03b17-nAChR-mediated neuroprotection.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Systemic administration of nicotine alleviated MPTP-induced behavioral symptoms, improved motor coordination, and protected against dopaminergic neuron loss and the activation of astrocytes and microglia in the substantia nigra. The protective effects of nicotine were abolished by administration of the \u03b17-nAChR-selective antagonist methyllycaconitine (MLA). In primary cultured mouse astrocytes, pretreatment with nicotine suppressed MPP<jats:sup>+<\/jats:sup>-induced or LPS-induced astrocyte activation, as evidenced by both decreased production of TNF-\u03b1 and inhibition of extracellular regulated kinase1\/2 (Erk1\/2) and p38 activation in astrocytes, and these effects were also reversed by MLA.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>Taken together, our results suggest that \u03b17-nAChR-mediated inhibition of astrocyte activation is an important mechanism underlying the protective effects of nicotine.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1742-2094-9-98","type":"journal-article","created":{"date-parts":[[2012,5,31]],"date-time":"2012-05-31T15:08:56Z","timestamp":1338476936000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":101,"title":["\u03b17 nicotinic acetylcholine 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