A novel α-conotoxin [D1G, ΔQ14] LvIC decreased mouse locomotor activity
Background and PurposeNicotinic 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. α-Conotoxins, which are peptides derived from t...
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Frontiers Media S.A.
2025-01-01
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2024.1466504/full |
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| author | Wen Wang Wen Wang Meiting Wang Huanbai Wang Weifeng Xu Conggang Wang Jie Pei Xiaodan Li Dongting Zhangsun Dongting Zhangsun |
| author_facet | Wen Wang Wen Wang Meiting Wang Huanbai Wang Weifeng Xu Conggang Wang Jie Pei Xiaodan Li Dongting Zhangsun Dongting Zhangsun |
| author_sort | Wen Wang |
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| description | Background and PurposeNicotinic 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. α-Conotoxins, which are peptides derived from the venom of marine cone snails, target different subtypes of nAChRs. Specifically, α-Conotoxins [D1G, ΔQ14] LvIC, identified from Conus lividus, have demonstrated strong activity on α6β4* nAChRs in vitro. However, the effects of [D1G, ΔQ14] LvIC have not been investigated in vivo. This study aims to examine the activities of [D1G, ΔQ14] LvIC and explore its potential mechanisms in vivo.MethodsThe study involved the injection of [D1G, ΔQ14] LvIC into the lateral cerebral ventricle (LV) of mice. Following this procedure, behavioral tests were conducted to assess changes in the mice’s behavior. To investigate the molecular alterations in the mice’s 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, ΔQ14] LvIC.ResultsThe injection of [D1G, ΔQ14] 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, ΔQ14] LvIC did not impair the learning and memory abilities of the mice.ConclusionOur findings indicate that α-conotoxin [D1G, ΔQ14] 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, ΔQ14] LvIC could modulate mice’s locomotor activity. However, further investigation is needed to understand the therapeutic effects of [D1G, ΔQ14] LvIC. |
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| institution | Kabale University |
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| language | English |
| publishDate | 2025-01-01 |
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| spelling | doaj-art-4d519ae1fb714e5387153bd124e9932e2025-01-21T08:36:49ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-01-011510.3389/fphar.2024.14665041466504A novel α-conotoxin [D1G, ΔQ14] LvIC decreased mouse locomotor activityWen Wang0Wen Wang1Meiting Wang2Huanbai Wang3Weifeng Xu4Conggang Wang5Jie Pei6Xiaodan Li7Dongting Zhangsun8Dongting Zhangsun9Key Laboratory of Tropical Biological Resources of Ministry of Education, School of Life and Health Science, Hainan University, Haikou, ChinaGuangxi Key Laboratory of Special Biomedicine, School of Medicine, Guangxi University, Nanning, ChinaGuangxi Key Laboratory of Special Biomedicine, School of Medicine, Guangxi University, Nanning, ChinaKey Laboratory of Tropical Biological Resources of Ministry of Education, School of Life and Health Science, Hainan University, Haikou, ChinaKey Laboratory of Tropical Biological Resources of Ministry of Education, School of Life and Health Science, Hainan University, Haikou, ChinaGuangxi Key Laboratory of Special Biomedicine, School of Medicine, Guangxi University, Nanning, ChinaGuangxi Key Laboratory of Special Biomedicine, School of Medicine, Guangxi University, Nanning, ChinaKey Laboratory of Tropical Biological Resources of Ministry of Education, School of Life and Health Science, Hainan University, Haikou, ChinaKey Laboratory of Tropical Biological Resources of Ministry of Education, School of Life and Health Science, Hainan University, Haikou, ChinaGuangxi Key Laboratory of Special Biomedicine, School of Medicine, Guangxi University, Nanning, ChinaBackground and PurposeNicotinic 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. α-Conotoxins, which are peptides derived from the venom of marine cone snails, target different subtypes of nAChRs. Specifically, α-Conotoxins [D1G, ΔQ14] LvIC, identified from Conus lividus, have demonstrated strong activity on α6β4* nAChRs in vitro. However, the effects of [D1G, ΔQ14] LvIC have not been investigated in vivo. This study aims to examine the activities of [D1G, ΔQ14] LvIC and explore its potential mechanisms in vivo.MethodsThe study involved the injection of [D1G, ΔQ14] LvIC into the lateral cerebral ventricle (LV) of mice. Following this procedure, behavioral tests were conducted to assess changes in the mice’s behavior. To investigate the molecular alterations in the mice’s 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, ΔQ14] LvIC.ResultsThe injection of [D1G, ΔQ14] 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, ΔQ14] LvIC did not impair the learning and memory abilities of the mice.ConclusionOur findings indicate that α-conotoxin [D1G, ΔQ14] 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, ΔQ14] LvIC could modulate mice’s locomotor activity. However, further investigation is needed to understand the therapeutic effects of [D1G, ΔQ14] LvIC.https://www.frontiersin.org/articles/10.3389/fphar.2024.1466504/fullα-conotoxin [D1G, ΔQ14] LvIClocomotor activityncs-1NLGN-3nAChRs |
| spellingShingle | Wen Wang Wen Wang Meiting Wang Huanbai Wang Weifeng Xu Conggang Wang Jie Pei Xiaodan Li Dongting Zhangsun Dongting Zhangsun A novel α-conotoxin [D1G, ΔQ14] LvIC decreased mouse locomotor activity Frontiers in Pharmacology α-conotoxin [D1G, ΔQ14] LvIC locomotor activity ncs-1 NLGN-3 nAChRs |
| title | A novel α-conotoxin [D1G, ΔQ14] LvIC decreased mouse locomotor activity |
| title_full | A novel α-conotoxin [D1G, ΔQ14] LvIC decreased mouse locomotor activity |
| title_fullStr | A novel α-conotoxin [D1G, ΔQ14] LvIC decreased mouse locomotor activity |
| title_full_unstemmed | A novel α-conotoxin [D1G, ΔQ14] LvIC decreased mouse locomotor activity |
| title_short | A novel α-conotoxin [D1G, ΔQ14] LvIC decreased mouse locomotor activity |
| title_sort | novel α conotoxin d1g δq14 lvic decreased mouse locomotor activity |
| topic | α-conotoxin [D1G, ΔQ14] LvIC locomotor activity ncs-1 NLGN-3 nAChRs |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2024.1466504/full |
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