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Krill Oil Alleviated Methamphetamine-Induced Memory Impairment via the MAPK Signaling Pathway and Dopaminergic Synapse Pathway
Methamphetamine (METH) abuse exerts severe harmful effects in multiple organs, especially the brain, and can induce cognitive dysfunction and memory deficits in humans. Krill oil is rich in polyunsaturated fatty acids, while its effect on METH-induced cognitive impairment and mental disorders, and t...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8586701/ https://www.ncbi.nlm.nih.gov/pubmed/34776973 http://dx.doi.org/10.3389/fphar.2021.756822 |
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author | Ru, Qin Tian, Xiang Xiong, Qi Xu, Congyue Chen, Lin Wu, Yuxiang |
author_facet | Ru, Qin Tian, Xiang Xiong, Qi Xu, Congyue Chen, Lin Wu, Yuxiang |
author_sort | Ru, Qin |
collection | PubMed |
description | Methamphetamine (METH) abuse exerts severe harmful effects in multiple organs, especially the brain, and can induce cognitive dysfunction and memory deficits in humans. Krill oil is rich in polyunsaturated fatty acids, while its effect on METH-induced cognitive impairment and mental disorders, and the underlying mechanism remain unknown. The aim of the present study was to investigate the protective effect of krill oil on METH-induced memory deficits and to explore the molecular mechanisms by using an integrated strategy of bioinformatics analysis and experimental verification. METH-exposed mice were treated with or without krill oil. Learning and memory functions were evaluated by the Morris water maze. The drug–component–target network was constructed in combination with network pharmacology. The predicted hub genes and pathways were validated by the Western blot technique. With krill oil treatment, memory impairment induced by METH was significantly improved. 210 predicted targets constituted the drug–compound–target network by network pharmacology analysis. 20 hub genes such as DRD2, MAPK3, CREB, BDNF, and caspase-3 were filtered out as the underlying mechanisms of krill oil on improving memory deficits induced by METH. The KEGG pathway and GO enrichment analyses showed that the MAPK signaling pathway, cAMP signaling pathway, and dopaminergic synapse pathway were involved in the neuroprotective effects of krill oil. In the hippocampus, DRD2, cleaved caspase-3, and γ-H2AX expression levels were significantly increased in the METH group but decreased in the krill oil–treated group. Meanwhile, krill oil enhanced the expressions of p-PKA, p-ERK1/2, and p-CREB. Our findings suggested that krill oil improved METH-induced memory deficits, and this effect may occur via the MAPK signaling pathway and dopaminergic synapse pathways. The combination of network pharmacology approaches with experimental validation may offer a useful tool to characterize the molecular mechanism of multicomponent complexes. |
format | Online Article Text |
id | pubmed-8586701 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-85867012021-11-13 Krill Oil Alleviated Methamphetamine-Induced Memory Impairment via the MAPK Signaling Pathway and Dopaminergic Synapse Pathway Ru, Qin Tian, Xiang Xiong, Qi Xu, Congyue Chen, Lin Wu, Yuxiang Front Pharmacol Pharmacology Methamphetamine (METH) abuse exerts severe harmful effects in multiple organs, especially the brain, and can induce cognitive dysfunction and memory deficits in humans. Krill oil is rich in polyunsaturated fatty acids, while its effect on METH-induced cognitive impairment and mental disorders, and the underlying mechanism remain unknown. The aim of the present study was to investigate the protective effect of krill oil on METH-induced memory deficits and to explore the molecular mechanisms by using an integrated strategy of bioinformatics analysis and experimental verification. METH-exposed mice were treated with or without krill oil. Learning and memory functions were evaluated by the Morris water maze. The drug–component–target network was constructed in combination with network pharmacology. The predicted hub genes and pathways were validated by the Western blot technique. With krill oil treatment, memory impairment induced by METH was significantly improved. 210 predicted targets constituted the drug–compound–target network by network pharmacology analysis. 20 hub genes such as DRD2, MAPK3, CREB, BDNF, and caspase-3 were filtered out as the underlying mechanisms of krill oil on improving memory deficits induced by METH. The KEGG pathway and GO enrichment analyses showed that the MAPK signaling pathway, cAMP signaling pathway, and dopaminergic synapse pathway were involved in the neuroprotective effects of krill oil. In the hippocampus, DRD2, cleaved caspase-3, and γ-H2AX expression levels were significantly increased in the METH group but decreased in the krill oil–treated group. Meanwhile, krill oil enhanced the expressions of p-PKA, p-ERK1/2, and p-CREB. Our findings suggested that krill oil improved METH-induced memory deficits, and this effect may occur via the MAPK signaling pathway and dopaminergic synapse pathways. The combination of network pharmacology approaches with experimental validation may offer a useful tool to characterize the molecular mechanism of multicomponent complexes. Frontiers Media S.A. 2021-10-29 /pmc/articles/PMC8586701/ /pubmed/34776973 http://dx.doi.org/10.3389/fphar.2021.756822 Text en Copyright © 2021 Ru, Tian, Xiong, Xu, Chen and Wu. https://creativecommons.org/licenses/by/4.0/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) and the copyright owner(s) 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. |
spellingShingle | Pharmacology Ru, Qin Tian, Xiang Xiong, Qi Xu, Congyue Chen, Lin Wu, Yuxiang Krill Oil Alleviated Methamphetamine-Induced Memory Impairment via the MAPK Signaling Pathway and Dopaminergic Synapse Pathway |
title | Krill Oil Alleviated Methamphetamine-Induced Memory Impairment via the MAPK Signaling Pathway and Dopaminergic Synapse Pathway |
title_full | Krill Oil Alleviated Methamphetamine-Induced Memory Impairment via the MAPK Signaling Pathway and Dopaminergic Synapse Pathway |
title_fullStr | Krill Oil Alleviated Methamphetamine-Induced Memory Impairment via the MAPK Signaling Pathway and Dopaminergic Synapse Pathway |
title_full_unstemmed | Krill Oil Alleviated Methamphetamine-Induced Memory Impairment via the MAPK Signaling Pathway and Dopaminergic Synapse Pathway |
title_short | Krill Oil Alleviated Methamphetamine-Induced Memory Impairment via the MAPK Signaling Pathway and Dopaminergic Synapse Pathway |
title_sort | krill oil alleviated methamphetamine-induced memory impairment via the mapk signaling pathway and dopaminergic synapse pathway |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8586701/ https://www.ncbi.nlm.nih.gov/pubmed/34776973 http://dx.doi.org/10.3389/fphar.2021.756822 |
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