{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T22:54:00Z","timestamp":1765234440760,"version":"3.37.3"},"reference-count":33,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2017,10,8]],"date-time":"2017-10-08T00:00:00Z","timestamp":1507420800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31400917"],"award-info":[{"award-number":["31400917"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2017,12]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Sigma\u20101 receptors (Sig\u20101Rs) are unique endoplasmic reticulum proteins that have been implicated in both neurodegenerative and ischemic diseases, such as Alzheimer's disease and stroke. Accumulating evidence has suggested that Sig\u20101R plays a role in neuroprotection and axon outgrowth. The underlying mechanisms of Sig\u20101R\u2010mediated neuroprotection have been well elucidated. However, the mechanisms underlying the effects of Sig\u20101R on axon outgrowth are not fully understood.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>To clarify this issue, we utilized immunofluorescence to compare the axon lengths of cultured na\u00efve hippocampal neurons before and after the application of the Sig\u20101R agonist, <jats:styled-content style=\"fixed-case\">SA<\/jats:styled-content>4503. Then, electrophysiology and immunofluorescence were used to examine voltage\u2010gated calcium ion channel (<jats:styled-content style=\"fixed-case\">VGCC<\/jats:styled-content>s) currents in the cell membranes and growth cones.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We found that Sig\u20101R activation dramatically enhanced the axonal length of the na\u00efve hippocampal neurons. Application of the Sig\u20101R antagonist <jats:styled-content style=\"fixed-case\">NE<\/jats:styled-content>100 and gene knockdown techniques both demonstrated the effects of Sig\u20101R. The growth\u2010promoting effect of <jats:styled-content style=\"fixed-case\">SA<\/jats:styled-content>4503 was accompanied by the inhibition of voltage\u2010gated Ca<jats:sup>2+<\/jats:sup> influx and was recapitulated by incubating the neurons with the L\u2010type, N\u2010type, and P\/Q\u2010type <jats:styled-content style=\"fixed-case\">VGCC<\/jats:styled-content> blockers, nimodipine, <jats:styled-content style=\"fixed-case\">MVIIA<\/jats:styled-content> and \u03c9\u2010agatoxin IVA, respectively. This effect was unrelated to glial cells. The application of <jats:styled-content style=\"fixed-case\">SA<\/jats:styled-content>4503 transformed the growth cone morphologies from complicated to simple, which favored axon outgrowth.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Sig\u20101R activation can enhance axon outgrowth and may have a substantial influence on neurogenesis and neurodegenerative diseases.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.12768","type":"journal-article","created":{"date-parts":[[2017,10,9]],"date-time":"2017-10-09T04:06:44Z","timestamp":1507522004000},"page":"930-939","source":"Crossref","is-referenced-by-count":23,"title":["Sigma\u20101 receptor agonist increases axon outgrowth of hippocampal neurons via voltage\u2010gated calcium ions channels"],"prefix":"10.1111","volume":"23","author":[{"given":"Dong","family":"Li","sequence":"first","affiliation":[{"name":"Department of Biochemical Pharmacology Beijing Institute of Pharmacology and Toxicology  Beijing 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