{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T16:14:05Z","timestamp":1753892045856,"version":"3.41.2"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,1,21]],"date-time":"2025-01-21T00:00:00Z","timestamp":1737417600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100014717","name":"National Outstanding Youth Science Fund Project of National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100014717","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>Nicotinic acetylcholine receptors (nAChRs), which are expressed throughout the mammalian brain, mediate a variety of physiological functions. Despite their widespread presence, the functions of nAChRs are not yet fully understood. \u03b1-Conotoxins, which are peptides derived from the venom of marine cone snails, target different subtypes of nAChRs. Specifically, \u03b1-Conotoxins [D1G, \u0394Q14] LvIC, identified from <jats:italic>Conus lividus<\/jats:italic>, have demonstrated strong activity on \u03b16\u03b24* nAChRs <jats:italic>in vitro<\/jats:italic>. However, the effects of [D1G, \u0394Q14] LvIC have not been investigated <jats:italic>in vivo<\/jats:italic>. This study aims to examine the activities of [D1G, \u0394Q14] LvIC and explore its potential mechanisms <jats:italic>in vivo<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The study involved the injection of [D1G, \u0394Q14] LvIC into the lateral cerebral ventricle (LV) of mice. Following this procedure, behavioral tests were conducted to assess changes in the mice\u2019s behavior. To investigate the molecular alterations in the mice\u2019s brains, untargeted metabolomics and label-free Liquid Chromatography-Tandem Mass Spectrometry (LC-MS\/MS) were employed. Subsequently, Western blot (WB) and quantitative reverse transcription PCR (RT-qPCR) techniques were utilized to detect specific molecular changes induced by [D1G, \u0394Q14] LvIC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The injection of [D1G, \u0394Q14] LvIC led to a decrease in locomotor activity in mice. This treatment also resulted in reduced expression of neuronal calcium sensor 1 (NCS-1) and neuroligin 3 (NLGN-3) in the prefrontal cortex (PFC), hippocampus (Hip), and caudate putamen (CPu). Both NCS-1 and NLGN-3 are crucial for neuronal development, synapse formation, and neuron activity, and their reduction is associated with decreased synapse strength. Despite these changes, results from the Morris water maze (MWM) indicated that [D1G, \u0394Q14] LvIC did not impair the learning and memory abilities of the mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our findings indicate that \u03b1-conotoxin [D1G, \u0394Q14] LvIC significantly decreased locomotor activity in mice. Additionally, it altered gene expression primarily in areas related to neuronal development, synapse formation, and neuron activity, while also reducing synapse strength. This study first proposed that [D1G, \u0394Q14] LvIC could modulate mice\u2019s locomotor activity. However, further investigation is needed to understand the therapeutic effects of [D1G, \u0394Q14] LvIC.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fphar.2024.1466504","type":"journal-article","created":{"date-parts":[[2025,1,21]],"date-time":"2025-01-21T08:38:00Z","timestamp":1737448680000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["A novel \u03b1-conotoxin [D1G, \u0394Q14] LvIC decreased mouse locomotor activity"],"prefix":"10.3389","volume":"15","author":[{"given":"Wen","family":"Wang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meiting","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huanbai","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weifeng","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Conggang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Pei","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaodan","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dongting","family":"Zhangsun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,1,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"5815","DOI":"10.1021\/cr400401e","article-title":"Discovery, synthesis, and structure-activity relationships of conotoxins","volume":"114","author":"Akondi","year":"2014","journal-title":"Chem. 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