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Combined administration of resolvin E1 and lipoxin A4 resolves inflammation in a murine model of Alzheimer's disease.
Kantarci, Alpdogan; Aytan, Nurgul; Palaska, Iro; Stephens, Danielle; Crabtree, Leah; Benincasa, Claudia; Jenkins, Bruce G; Carreras, Isabel; Dedeoglu, Alpaslan.
Afiliação
  • Kantarci A; Forsyth Institute, 245 First Street, Cambridge, MA 02142, USA. Electronic address: akantarci@forsyth.org.
  • Aytan N; Department of Veterans Affairs, VA Boston Healthcare System, Boston, MA 02130, USA; Department of Neurology, Boston University School of Medicine, Boston, MA 02118, USA; Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA. Electronic address: naytan
  • Palaska I; Forsyth Institute, 245 First Street, Cambridge, MA 02142, USA. Electronic address: iro.palaska@gmail.com.
  • Stephens D; Forsyth Institute, 245 First Street, Cambridge, MA 02142, USA. Electronic address: dstephens@forsyth.org.
  • Crabtree L; Department of Veterans Affairs, VA Boston Healthcare System, Boston, MA 02130, USA; Department of Neurology, Boston University School of Medicine, Boston, MA 02118, USA; University of Exeter Medical School, Devon, EX4 4QJ, UK. Electronic address: lc473@exeter.ac.uk.
  • Benincasa C; Department of Veterans Affairs, VA Boston Healthcare System, Boston, MA 02130, USA. Electronic address: cbenin@bu.edu.
  • Jenkins BG; Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA. Electronic address: bgj@nmr.mgh.harvard.edu.
  • Carreras I; Department of Veterans Affairs, VA Boston Healthcare System, Boston, MA 02130, USA; Department of Neurology, Boston University School of Medicine, Boston, MA 02118, USA; Department of Biochemistry, Boston University School of Medicine, Boston, MA 02118, USA. Electronic address: carreras@bu.edu.
  • Dedeoglu A; Department of Veterans Affairs, VA Boston Healthcare System, Boston, MA 02130, USA; Department of Neurology, Boston University School of Medicine, Boston, MA 02118, USA; Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA. Electronic address: dedeog
Exp Neurol ; 300: 111-120, 2018 02.
Article em En | MEDLINE | ID: mdl-29126887
Dysfunction in the resolution of inflammation may play a key role in Alzheimer's disease (AD). In this study, we found that the levels of specialized pro-resolving lipid mediators (SPMs) in the hippocampus of 5xFAD mice are significantly lower than in non-transgenic littermates. We, therefore, tested the hypothesis that treatment with resolvin E1 (RvE1) and lipoxin A4 (LXA4) alone or in combination will reverse the neuroinflammatory process and decrease Aß pathology. 5xFAD mice were treated intraperitoneally starting at 1month of age with RvE1 or LXA4 alone or in combination at a dose of 1.5 µg/kg, 3 times a week until 3months of age. We found that treatment with RvE1 or LXA4 alone or in combination increased the concentration of RvE1, LXA4, and RvD2 in the hippocampus as measured by ELISA. Combination treatment of RvE1 and LXA4 had a more potent effect on the activation of microglia and astrocytes than either treatment alone, measured by immunohistochemistry with Iba1 and GFAP antibodies, respectively. The concentrations of Aß40 and Aß42 were measured by ELISA and the percentage of Aß plaques were analyzed by immunohistochemistry. All treatments single and in combination, decreased the measures of Aß pathology and restored the homeostasis reversing the inflammatory process for inflammatory cytokines and chemokines (GM-CSF, IFN-γ, IL-1ß, IL-6, IL-10, TNF-α, MCP-1, MIP-1α, MIP-1ß, and RANTES) as measured by multiplex immunoassay. Overall, the study showed that the levels of SPMs in the hippocampus of 5xFAD mice were significantly lower than in wild-type mice; that treatment with RvE1 and LXA4 restored the level of these compounds, reversed the inflammatory process, and decreased the neuroinflammation associated with Aß pathology in 5xFAD mice.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Anti-Inflamatórios não Esteroides / Ácido Eicosapentaenoico / Lipoxinas / Modelos Animais de Doenças / Doença de Alzheimer Limite: Animals Idioma: En Revista: Exp Neurol Ano de publicação: 2018 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Anti-Inflamatórios não Esteroides / Ácido Eicosapentaenoico / Lipoxinas / Modelos Animais de Doenças / Doença de Alzheimer Limite: Animals Idioma: En Revista: Exp Neurol Ano de publicação: 2018 Tipo de documento: Article