Anti-neuroinflammatory effects of SLOH in Aβ-induced BV-2 microglial cells and 3xTg-AD mice involve the inhibition of GSK-3β. (20th November 2018)

• Record Type: Journal Article
• Authors: Wu, Xiaoli; Kosaraju, Jayasankar; Tam, Kin Yip
• Is Part Of: Neuroscience letters. Volume 687(2018)
• Page Start: 207
• Page End: 215
• Publication Date: 2018-11-20
• Subjects: Aβ Amyloid beta -- AD Alzheimer's disease -- ANOVA Analysis of variance -- BBB Blood-brain barrier -- BCA Bicinchoninic acid -- BSA Bovine serum albumin -- COX-2 Cyclooxygenase-2 -- DAPI 4′, 6-Diamidine-2′-phenylindole dihydrochloride -- DMEM Dulbecco's modified Eagle medium -- DMSO Dimethyl sulfoxide -- ECL Electrochemiluminescence -- EDTA Ethylenediaminetetraacetic acid -- EGTA Ethylene glycol tetraacetic acid -- ELISA Enzyme-linked immunosorbent assay -- FBS Fetal bovine serum -- GAPDH Glyceraldehyde 3-phosphate dehydrogenase -- GSK-3β Glycogen synthase kinase-3β -- HFIP 1, 1, 1, 3, 3, 3-hexafluoro-2-propanol -- HRP Horseradish peroxidase -- IL-1β Interleukin-1β -- IL-6 Interleukin-6 -- IL-10 Interleukin-10 -- iNOS Inducible nitric oxide synthase -- NFTs Neurofibrillary tangles -- NO Nitric oxide -- NP-40 Nonyl phenoxypolyethoxylethanol-40 -- PBS Phosphate-buffered saline -- PMSF Phenylmethanesulfonyl fluoride -- PVDF Polyvinylidene difluoride -- SDS-PAGE Sodium dodecyl sulfate-polyacrylamide gel electrophoresis -- SEM Standard error mean -- TBS Tris-buffered saline -- (TNF)-α Tumor necrosis factor-α; SLOH -- BV-2 cells -- 3xTg-AD mice -- Neuroinflammation -- GSK-3β; Neurology -- Periodicals; Neurology -- Periodicals; Research -- Periodicals; Neurologie -- Périodiques; Neuroanatomie -- Périodiques; Neuropharmacologie -- Périodiques; Neurophysiologie -- Périodiques; Neurology; Periodicals; Electronic journals; 617.48
• DOI: 10.1016/j.neulet.2018.09.056
• Languages: English
• ISSNs: 0304-3940

Abstract

Highlights: SLOH exhibited anti-neuroinflammatory effects in a BV-2 microglial cell model. SLOH reduced the number of Iba1-positive cells in triple transgenic AD mouse brains. SLOH attenuated the neuroinflammation through down-regulating the activity of GSK-3β. Abstract: Neuroinflammation has been observed in post-mortem Alzheimer's disease (AD) brains which could be due to Aβ interacting with microglia and astrocytes. SLOH, a carbazole-based fluorophore, was shown to bind to Aβ peptides. Herein, we investigated the anti-neuroinflammatory effects of SLOH using a BV-2 microglial cell model and a triple transgenic AD (3xTg-AD) mouse model. BV-2 cells were incubated with Aβ in the presence of SLOH for 24 h. The levels of pro-inflammatory and anti-inflammatory cytokines were determined. Moreover, 3xTg-AD mice were administrated with SLOH (2 mg kg −1 ) for one month. The mice were then sacrificed and the brains were used to assess the levels of pro-inflammatory, anti-inflammatory cytokines and the activation of ionized calcium-binding adapter molecule 1 (Iba1). BV-2 cell studies suggested that SLOH reduced the production and mRNA levels of pro-inflammatory cytokines TNF-α, IL-1β, COX-2, iNOS, and increased IL-10. Animal study confirmed that SLOH reduced the production of pro-inflammatory cytokines and increased the level of anti-inflammatory cytokine. Moreover, SLOH inhibited the activity of GSK-3β. In 3xTg-AD mouse model, SLOH treatment significantly decreased the number of Iba1-positive cells in mouse brains. Our results demonstrated that SLOH significantly attenuated the neuroinflammation through down-regulating the activity of GSK-3β.