• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

肽LCGA-17减轻创伤后应激障碍和抑郁症啮齿动物模型中的行为和神经化学缺陷。

Peptide LCGA-17 Attenuates Behavioral and Neurochemical Deficits in Rodent Models of PTSD and Depression.

作者信息

Malyshev Anton V, Sukhanova Iuliia A, Ushakova Valeria M, Zorkina Yana A, Abramova Olga V, Morozova Anna Y, Zubkov Eugene A, Mitkin Nikita A, Pavshintsev Vsevolod V, Doronin Igor I, Gedzun Vasilina R, Babkin Gennady A, Sanchez Sergio A, Baker Miah D, Haile Colin N

机构信息

Lactocore Inc., Newton, MA 02460, USA.

Department of Basic and Applied Neurobiology, V.P. Serbsky Federal Medical Research Centre of Psychiatry and Narcology, 119034 Moscow, Russia.

出版信息

Pharmaceuticals (Basel). 2022 Apr 12;15(4):462. doi: 10.3390/ph15040462.

DOI:10.3390/ph15040462
PMID:35455459
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9029485/
Abstract

We have previously described the LCGA-17 peptide as a novel anxiolytic and antidepressant candidate that acts through the α2δ VGCC (voltage-gated calcium channel) subunit with putative synergism with GABA-A receptors. The current study tested the potential efficacy of acute and chronic intranasal (i.n.) LCGA-17 (0.05 mg/kg and 0.5 mg/kg) in rats on predator odor-induced conditioned place aversion (POCPA), a model of post-traumatic stress disorder (PTSD), and chronic unpredictable stress (CUS) that produce a range of behavioral and physiological changes that parallel symptoms of depression in humans. CUS and LCGA-17 treatment effects were tested in the sucrose preference (SPT) social interaction (SI), female urine sniffing (FUST), novelty-suppressed feeding (NSFT), and forced swim (FST) tests. Analysis of the catecholamines content in brain structures after CUS was carried out using HPLC. The efficacy of i.n. LCGA-17 was also assessed using the Elevated plus-maze (EPM) and FST. Acute LCGA-17 administration showed anxiolytic and antidepressant effects in EPM and FST, similar to diazepam and ketamine, respectively. In the POCPA study, LCGA-17 significantly reduced place aversion, with efficacy greater than doxazosin. After CUS, chronic LCGA-17 administration reversed stress-induced alterations in numerous behavioral tests (SI, FUST, SPT, and FST), producing significant anxiolytic and antidepressant effects. Finally, LCGA-17 restored the norepinephrine levels in the hippocampus following stress. Together, these results support the further development of the LCGA-17 peptide as a rapid-acting anxiolytic and antidepressant.

摘要

我们之前曾将LCGA-17肽描述为一种新型抗焦虑和抗抑郁候选药物，它通过α2δ电压门控钙通道（VGCC）亚基发挥作用，并可能与GABA-A受体协同作用。当前研究测试了急性和慢性鼻内给予大鼠LCGA-17（0.05 mg/kg和0.5 mg/kg）对捕食者气味诱导的条件性位置厌恶（POCPA）、创伤后应激障碍（PTSD）模型以及慢性不可预测应激（CUS）的潜在疗效，CUS会产生一系列行为和生理变化，类似于人类抑郁症的症状。在蔗糖偏好（SPT）、社交互动（SI）、雌性尿液嗅探（FUST）、新奇抑制摄食（NSFT）和强迫游泳（FST）测试中检测了CUS和LCGA-17的治疗效果。使用高效液相色谱法（HPLC）分析CUS后脑结构中的儿茶胺含量。还使用高架十字迷宫（EPM）和FST评估了鼻内给予LCGA-17的疗效。急性给予LCGA-17在EPM和FST中分别显示出抗焦虑和抗抑郁作用，类似于地西泮和氯胺酮。在POCPA研究中，LCGA-17显著降低了位置厌恶，疗效优于多沙唑嗪。CUS后，慢性给予LCGA-17逆转了应激诱导的多项行为测试（SI、FUST、SPT和FST）中的改变，产生了显著的抗焦虑和抗抑郁作用。最后，LCGA-17恢复了应激后海马体中的去甲肾上腺素水平。总之，这些结果支持进一步开发LCGA-17肽作为一种速效抗焦虑和抗抑郁药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8765/9029485/e371828659b1/pharmaceuticals-15-00462-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8765/9029485/e7b8e22eca0d/pharmaceuticals-15-00462-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8765/9029485/149ff1d966f5/pharmaceuticals-15-00462-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8765/9029485/d43c74bd1fea/pharmaceuticals-15-00462-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8765/9029485/9745bb4f8437/pharmaceuticals-15-00462-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8765/9029485/1c71facf2e0e/pharmaceuticals-15-00462-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8765/9029485/32ff88436797/pharmaceuticals-15-00462-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8765/9029485/8f8d9d247c1a/pharmaceuticals-15-00462-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8765/9029485/d73aa8860bf6/pharmaceuticals-15-00462-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8765/9029485/6a8f48d6d91a/pharmaceuticals-15-00462-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8765/9029485/e371828659b1/pharmaceuticals-15-00462-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8765/9029485/e7b8e22eca0d/pharmaceuticals-15-00462-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8765/9029485/149ff1d966f5/pharmaceuticals-15-00462-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8765/9029485/d43c74bd1fea/pharmaceuticals-15-00462-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8765/9029485/9745bb4f8437/pharmaceuticals-15-00462-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8765/9029485/1c71facf2e0e/pharmaceuticals-15-00462-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8765/9029485/32ff88436797/pharmaceuticals-15-00462-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8765/9029485/8f8d9d247c1a/pharmaceuticals-15-00462-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8765/9029485/d73aa8860bf6/pharmaceuticals-15-00462-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8765/9029485/6a8f48d6d91a/pharmaceuticals-15-00462-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8765/9029485/e371828659b1/pharmaceuticals-15-00462-g010.jpg

相似文献

1
Peptide LCGA-17 Attenuates Behavioral and Neurochemical Deficits in Rodent Models of PTSD and Depression.肽LCGA-17减轻创伤后应激障碍和抑郁症啮齿动物模型中的行为和神经化学缺陷。
Pharmaceuticals (Basel). 2022 Apr 12;15(4):462. doi: 10.3390/ph15040462.
2
Screening and Behavioral Validation of a Novel Peptide, LCGA-17, With Anxiolytic-Like Properties.一种具有抗焦虑样特性的新型肽LCGA - 17的筛选与行为验证
Front Neurosci. 2021 Aug 2;15:705590. doi: 10.3389/fnins.2021.705590. eCollection 2021.
3
L-type calcium channel regulation of depression, anxiety and anhedonia-related behavioral phenotypes following chronic stress exposure.慢性应激暴露后，L 型钙通道对抑郁、焦虑和快感缺失相关行为表型的调节。
Neuropharmacology. 2024 Oct 1;257:110031. doi: 10.1016/j.neuropharm.2024.110031. Epub 2024 Jun 12.
4
Fraxetin attenuates disrupted behavioral and central neurochemical activity in a model of chronic unpredictable stress.在慢性不可预测应激模型中，紫铆亭可减轻行为紊乱和中枢神经化学活性。
Front Pharmacol. 2023 Mar 23;14:1135497. doi: 10.3389/fphar.2023.1135497. eCollection 2023.
5
Involvement of norepinephrine and serotonin system in antidepressant-like effects of hederagenin in the rat model of unpredictable chronic mild stress-induced depression.去甲肾上腺素和5-羟色胺系统在常春藤皂苷元对不可预测慢性轻度应激诱导的大鼠抑郁模型的抗抑郁样作用中的参与
Pharm Biol. 2015 Mar;53(3):368-77. doi: 10.3109/13880209.2014.922586. Epub 2014 Dec 4.
6
S 47445 Produces Antidepressant- and Anxiolytic-Like Effects through Neurogenesis Dependent and Independent Mechanisms.S 47445 通过神经发生依赖性和非依赖性机制产生抗抑郁和抗焦虑样作用。
Front Pharmacol. 2017 Jul 19;8:462. doi: 10.3389/fphar.2017.00462. eCollection 2017.
7
Testosterone has antidepressant-like efficacy and facilitates imipramine-induced neuroplasticity in male rats exposed to chronic unpredictable stress.睾酮对暴露于慢性不可预测应激的雄性大鼠具有抗抑郁样功效，并促进丙咪嗪诱导的神经可塑性。
Horm Behav. 2016 Mar;79:58-69. doi: 10.1016/j.yhbeh.2016.01.001. Epub 2016 Jan 14.
8
Antidepressant effects of fibroblast growth factor-2 in behavioral and cellular models of depression.成纤维细胞生长因子-2 在抑郁的行为和细胞模型中的抗抑郁作用。
Biol Psychiatry. 2012 Aug 15;72(4):258-65. doi: 10.1016/j.biopsych.2012.03.003. Epub 2012 Apr 17.
9
Puerarin ameliorated the behavioral deficits induced by chronic stress in rats.葛根素改善了慢性应激诱导的大鼠行为缺陷。
Sci Rep. 2017 Jul 24;7(1):6266. doi: 10.1038/s41598-017-06552-x.
10
Efficacy and Anti-Inflammatory Activity of Ashwagandha Sustained-Release Formulation on Depression and Anxiety Induced by Chronic Unpredictable Stress: in vivo and in vitro Studies.南非醉茄缓释制剂对慢性不可预测应激诱导的抑郁和焦虑的疗效及抗炎活性：体内和体外研究
J Exp Pharmacol. 2023 Jul 25;15:291-305. doi: 10.2147/JEP.S407906. eCollection 2023.

引用本文的文献

1
Association between psychiatric disorders and the risk of stroke: a meta-analysis of cohort studies.精神障碍与中风风险之间的关联：队列研究的荟萃分析
Front Neurol. 2024 Dec 18;15:1444862. doi: 10.3389/fneur.2024.1444862. eCollection 2024.
2
The Novel Peptide Chm-273s Has Therapeutic Potential for Metabolic Disorders: Evidence from In Vitro Studies and High-Sucrose Diet and High-Fat Diet Rodent Models.新型肽Chm-273s对代谢紊乱具有治疗潜力：来自体外研究以及高糖饮食和高脂饮食啮齿动物模型的证据。
Pharmaceutics. 2022 Sep 30;14(10):2088. doi: 10.3390/pharmaceutics14102088.

本文引用的文献

1
Brain Metabolic Profile after Intranasal vs. Intraperitoneal Clomipramine Treatment in Rats with Ultrasound Model of Depression.脑代谢谱在抑郁超声模型大鼠经鼻内与腹腔给予氯米帕明后的变化。
Int J Mol Sci. 2021 Sep 4;22(17):9598. doi: 10.3390/ijms22179598.
2
Screening and Behavioral Validation of a Novel Peptide, LCGA-17, With Anxiolytic-Like Properties.一种具有抗焦虑样特性的新型肽LCGA - 17的筛选与行为验证
Front Neurosci. 2021 Aug 2;15:705590. doi: 10.3389/fnins.2021.705590. eCollection 2021.
3
Repeated stress exposure in mid-adolescence attenuates behavioral, noradrenergic, and epigenetic effects of trauma-like stress in early adult male rats.
在青春期中期反复暴露于应激环境中会减弱成年早期雄性大鼠类似创伤性应激的行为、去甲肾上腺素能和表观遗传效应。
Sci Rep. 2020 Oct 21;10(1):17935. doi: 10.1038/s41598-020-74481-3.
4
[Molecular Biological Aspects of Depressive Disorders: A Modern View].[抑郁症的分子生物学方面：现代观点]
Mol Biol (Mosk). 2020 Sep-Oct;54(5):725-749. doi: 10.31857/S0026898420050110.
5
Depression in post-traumatic stress disorder.创伤后应激障碍中的抑郁。
Rev Neurosci. 2020 Oct 25;31(7):703-722. doi: 10.1515/revneuro-2020-0006.
6
Diazepam limits microglia-mediated neuronal remodeling in the prefrontal cortex and associated behavioral consequences following chronic unpredictable stress.地西泮可限制慢性不可预测应激后前额叶皮质中小胶质细胞介导的神经元重塑及相关行为后果。
Neuropsychopharmacology. 2020 Sep;45(10):1766-1776. doi: 10.1038/s41386-020-0720-1. Epub 2020 May 26.
7
NLRP1-Mediated Antidepressant Effect of Ketamine in Chronic Unpredictable Mild Stress Model in Rats.NLRP1介导的氯胺酮对大鼠慢性不可预测轻度应激模型的抗抑郁作用。
Psychiatry Investig. 2020 Apr;17(4):283-291. doi: 10.30773/pi.2019.0189. Epub 2020 Mar 24.
8
Gender- and Sex-Based Contributors to Sex Differences in PTSD.性别和基于性别的因素对 PTSD 性别差异的影响。
Curr Psychiatry Rep. 2020 Mar 3;22(4):19. doi: 10.1007/s11920-020-1140-y.
9
An Open-Label Study of Doxazosin Extended-Release for PTSD: Findings and Recommendations for Future Research on Doxazosin.一项关于多沙唑嗪缓释片治疗创伤后应激障碍的开放标签研究：多沙唑嗪未来研究的结果与建议
Focus (Am Psychiatr Publ). 2018 Jan;16(1):67-73. doi: 10.1176/appi.focus.20170031. Epub 2018 Jan 24.
10
Pharmacological prevention and early treatment of post-traumatic stress disorder and acute stress disorder: a systematic review and meta-analysis.药物预防和早期治疗创伤后应激障碍和急性应激障碍：系统评价和荟萃分析。
Transl Psychiatry. 2019 Dec 9;9(1):334. doi: 10.1038/s41398-019-0673-5.