Full metadata record
DC Field | Value | Language |
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dc.contributor.author | Kim, Jieun | - |
dc.contributor.author | Lee, Hyun-ju | - |
dc.contributor.author | Park, Jin-Hee | - |
dc.contributor.author | Cha, Byung-Yoon | - |
dc.contributor.author | Hoe, Hyang-Sook | - |
dc.date.accessioned | 2022-11-03T08:00:01Z | - |
dc.date.available | 2022-11-03T08:00:01Z | - |
dc.date.created | 2022-08-08 | - |
dc.date.issued | 2022-07 | - |
dc.identifier.issn | 1742-2094 | - |
dc.identifier.uri | http://hdl.handle.net/20.500.11750/17042 | - |
dc.description.abstract | Background: In chronic myelogenous leukemia, reciprocal translocation between chromosome 9 and chromosome 22 generates a chimeric protein, Bcr-Abl, that leads to hyperactivity of tyrosine kinase-linked signaling transduction. The therapeutic agent nilotinib inhibits Bcr-Abl/DDR1 and can cross the blood–brain barrier, but its potential impact on neuroinflammatory responses and cognitive function has not been studied in detail. Methods: The effects of nilotinib in vitro and in vivo were assessed by a combination of RT-PCR, real-time PCR, western blotting, ELISA, immunostaining, and/or subcellular fractionation. In the in vitro experiments, the effects of 200ng/mL LPS or PBS on BV2 microglial cells, primary microglia or primary astrocytes pre- or post-treated with 5µM nilotinib or vehicle were evaluated. The in vivo experiments involved wild-type mice administered a 7-day course of daily injections with 20mg/kg nilotinib (i.p.) or vehicle before injection with 10mg/kg LPS (i.p.) or PBS. Results: In BV2 microglial cells, pre- and post-treatment with nilotinib altered LPS-induced proinflammatory/anti-inflammatory cytokine mRNA levels by suppressing AKT/P38/SOD2 signaling. Nilotinib treatment also significantly downregulated LPS-stimulated proinflammatory cytokine levels in primary microglia and primary astrocytes by altering P38/STAT3 signaling. Experiments in wild-type mice showed that nilotinib administration affected LPS-mediated microglial/astroglial activation in a brain region-specific manner in vivo. In addition, nilotinib significantly reduced proinflammatory cytokine IL-1β, IL-6 and COX-2 levels and P38/STAT3 signaling in the brain in LPS-treated wild-type mice. Importantly, nilotinib treatment rescued LPS-mediated spatial working memory impairment and cortical dendritic spine number in wild-type mice. Conclusions: Our results indicate that nilotinib can modulate neuroinflammatory responses and cognitive function in LPS-stimulated wild-type mice. © 2022, The Author(s). | - |
dc.language | English | - |
dc.publisher | BioMed Central | - |
dc.title | Nilotinib modulates LPS-induced cognitive impairment and neuroinflammatory responses by regulating P38/STAT3 signaling | - |
dc.type | Article | - |
dc.identifier.doi | 10.1186/s12974-022-02549-0 | - |
dc.identifier.scopusid | 2-s2.0-85134226859 | - |
dc.identifier.bibliographicCitation | Journal of Neuroinflammation, v.19, no.1 | - |
dc.description.isOpenAccess | TRUE | - |
dc.subject.keywordAuthor | Cognitive function | - |
dc.subject.keywordAuthor | LPS | - |
dc.subject.keywordAuthor | Microglia | - |
dc.subject.keywordAuthor | Nilotinib | - |
dc.subject.keywordAuthor | p38 | - |
dc.subject.keywordAuthor | SOD2 | - |
dc.subject.keywordAuthor | STAT3 | - |
dc.subject.keywordPlus | TYROSINE KINASE INHIBITOR | - |
dc.subject.keywordPlus | MEMORY IMPAIRMENT | - |
dc.subject.keywordPlus | OXIDATIVE-STRESS | - |
dc.subject.keywordPlus | MICROGLIA | - |
dc.subject.keywordPlus | INFLAMMATION | - |
dc.subject.keywordPlus | ACTIVATION | - |
dc.subject.keywordPlus | INTERLEUKIN-1-BETA | - |
dc.subject.keywordPlus | IMMUNOREACTIVITY | - |
dc.subject.keywordPlus | DISEASE | - |
dc.citation.number | 1 | - |
dc.citation.title | Journal of Neuroinflammation | - |
dc.citation.volume | 19 | - |
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