Skip to main content

ORIGINAL RESEARCH article

Front. Pharmacol.
Sec. Experimental Pharmacology and Drug Discovery
Volume 15 - 2024 | doi: 10.3389/fphar.2024.1466504

A Novel α-Conotoxin [D1G, ΔQ14] LvIC Decreased Mouse Locomotor Activity

Provisionally accepted
Wen Wang Wen Wang 1Meiting Wang Meiting Wang 2*Huanbai Wang Huanbai Wang 1*Weifeng Xu Weifeng Xu 1*Conggang Wang Conggang Wang 2*Jie Pei Jie Pei 2*Xiaodan Li Xiaodan Li 1*Dongting Zhangsun Dongting Zhangsun 1*
  • 1 Hainan University, Haikou, China
  • 2 Guangxi University, Nanning, Guangxi Zhuang Region, China

The final, formatted version of the article will be published soon.

    Background and Purpose: 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. 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. Methods: The 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. Results: The 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. Conclusion: Our 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.

    Keywords: α-Conotoxin [D1G, ΔQ14] LvIC, locomotor activity, ncs-1, NLGN-3

    Received: 18 Jul 2024; Accepted: 13 Dec 2024.

    Copyright: © 2024 Wang, Wang, Wang, Xu, Wang, Pei, Li and Zhangsun. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Meiting Wang, Guangxi University, Nanning, Guangxi Zhuang Region, China
    Huanbai Wang, Hainan University, Haikou, China
    Weifeng Xu, Hainan University, Haikou, China
    Conggang Wang, Guangxi University, Nanning, Guangxi Zhuang Region, China
    Jie Pei, Guangxi University, Nanning, Guangxi Zhuang Region, China
    Xiaodan Li, Hainan University, Haikou, China
    Dongting Zhangsun, Hainan University, Haikou, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.