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Article: Potential link between the RagA-mTOR-p70S6K axis and depressive-behaviors during bacterial liposaccharide challenge

TitlePotential link between the RagA-mTOR-p70S6K axis and depressive-behaviors during bacterial liposaccharide challenge
Authors
KeywordsDepression
LPS
RagA
mTOR
p70S6K
Issue Date2019
PublisherBioMed Central Ltd. The Journal's web site is located at http://www.jneuroinflammation.com/home/
Citation
Journal of Neuroinflammation, 2019, v. 16, p. article no. 211 How to Cite?
AbstractBackground: Bacterial infection is a potential risk factor for depression. However, little is known about the mechanistic link between bacterial endotoxin and depressive-like behaviors. The aim of the present study was to clarify whether liposaccharide (LPS) could induce depressive-like behaviors in mice via sequentially activating small GTPase RagA, mammalian target of rapamycin (mTOR), and p70S6K. Methods: C57BL/6 N mice were treated with 0.83 mg/kg LPS by intraperitoneal injection for 24 h. The animals were assessed for depressive-like behaviors by forced swim test and tail suspension test. The expression levels of RagA, mTOR, and p70S6K were determined in mice, primary cortical neurons, neural stem cells, and PC12 cells. Results: LPS effectively induced depressive-like behaviors in mice. Biochemical examination revealed that LPS not only upregulated RagA expression but also activated mTOR/p70S6K pathway in mouse brains. LPS challenge also achieved a similar effect in primary cortical neurons, neural stem cells, and PC12 cells. Following the silencing of RagA expression with specific siRNA, LPS failed to induce mTORC1 translocation to the lysosomal membranes in PC12 cells. These results suggested that LPS might sequentially upregulate RagA and activate mTOR and p70S6K pathways in mice and neural stem cells. Conclusions: This study for the first time demonstrated that LPS might induce depressive-like behaviors in mice via the upregulation of RagA and subsequent activation of mTOR/p70S6K pathway. Such information may highlight the RagA-mTOR-p70S6K signaling cascade as a novel therapeutic target for the development of new anti-depressant therapeutics.
Persistent Identifierhttp://hdl.handle.net/10722/283706
ISSN
2018 Impact Factor: 5.7
2015 SCImago Journal Rankings: 2.538
PubMed Central ID

 

DC FieldValueLanguage
dc.contributor.authorZhao, J-
dc.contributor.authorLao, L-
dc.contributor.authorCui, W-
dc.contributor.authorRong, J-
dc.date.accessioned2020-07-03T08:22:57Z-
dc.date.available2020-07-03T08:22:57Z-
dc.date.issued2019-
dc.identifier.citationJournal of Neuroinflammation, 2019, v. 16, p. article no. 211-
dc.identifier.issn1742-2094-
dc.identifier.urihttp://hdl.handle.net/10722/283706-
dc.description.abstractBackground: Bacterial infection is a potential risk factor for depression. However, little is known about the mechanistic link between bacterial endotoxin and depressive-like behaviors. The aim of the present study was to clarify whether liposaccharide (LPS) could induce depressive-like behaviors in mice via sequentially activating small GTPase RagA, mammalian target of rapamycin (mTOR), and p70S6K. Methods: C57BL/6 N mice were treated with 0.83 mg/kg LPS by intraperitoneal injection for 24 h. The animals were assessed for depressive-like behaviors by forced swim test and tail suspension test. The expression levels of RagA, mTOR, and p70S6K were determined in mice, primary cortical neurons, neural stem cells, and PC12 cells. Results: LPS effectively induced depressive-like behaviors in mice. Biochemical examination revealed that LPS not only upregulated RagA expression but also activated mTOR/p70S6K pathway in mouse brains. LPS challenge also achieved a similar effect in primary cortical neurons, neural stem cells, and PC12 cells. Following the silencing of RagA expression with specific siRNA, LPS failed to induce mTORC1 translocation to the lysosomal membranes in PC12 cells. These results suggested that LPS might sequentially upregulate RagA and activate mTOR and p70S6K pathways in mice and neural stem cells. Conclusions: This study for the first time demonstrated that LPS might induce depressive-like behaviors in mice via the upregulation of RagA and subsequent activation of mTOR/p70S6K pathway. Such information may highlight the RagA-mTOR-p70S6K signaling cascade as a novel therapeutic target for the development of new anti-depressant therapeutics.-
dc.languageeng-
dc.publisherBioMed Central Ltd. The Journal's web site is located at http://www.jneuroinflammation.com/home/-
dc.relation.ispartofJournal of Neuroinflammation-
dc.rightsJournal of Neuroinflammation. Copyright © BioMed Central Ltd.-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectDepression-
dc.subjectLPS-
dc.subjectRagA-
dc.subjectmTOR-
dc.subjectp70S6K-
dc.titlePotential link between the RagA-mTOR-p70S6K axis and depressive-behaviors during bacterial liposaccharide challenge-
dc.typeArticle-
dc.identifier.emailZhao, J: zhaojia7@hku.hk-
dc.identifier.emailLao, L: lxlao1@hku.hk-
dc.identifier.emailRong, J: jrong@hku.hk-
dc.identifier.authorityLao, L=rp01784-
dc.identifier.authorityRong, J=rp00515-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1186/s12974-019-1610-5-
dc.identifier.pmid31711501-
dc.identifier.pmcidPMC6844034-
dc.identifier.scopuseid_2-s2.0-85074859341-
dc.identifier.hkuros310728-
dc.identifier.volume16-
dc.identifier.spagearticle no. 211-
dc.identifier.epagearticle no. 211-
dc.publisher.placeUnited Kingdom-

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