Combined 1-Deoxynojirimycin and Ibuprofen Treatment Decreases Microglial Activation, Phagocytosis and Dopaminergic Degen
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ORIGINAL ARTICLE
Combined 1-Deoxynojirimycin and Ibuprofen Treatment Decreases Microglial Activation, Phagocytosis and Dopaminergic Degeneration in MPTP-Treated Mice TCS Costa 1,2 & E Fernandez-Villalba 1 & V. Izura 1 & AM Lucas-Ochoa 1 & NJ Menezes-Filho 2 & RC Santana 3 & MD de Oliveira 2,4 & FM Araújo 1,2 & C Estrada 1 & VDA Silva 2 & SL Costa 2 & MT Herrero 1 Received: 3 February 2020 / Accepted: 14 May 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Inflammation is a predominant aspect of neurodegenerative diseases and experimental studies performed in animal models of Parkinson’s disease (PD) suggesting that a sustained neuroinflammation exacerbates the nigrostriatal degeneration pathway. The central role of microglia in neuroinflammation has been studied as a target for potential neuroprotective drugs for PD, for example nonsteroidal anti-inflammatory drugs (NSAIDs) and matrix metalloproteinases (MMP) inhibitors that regulates microglial activation and migration. The aim of this study was to investigate the neuroprotective response of the iminosugar 1-deoxynojirimycin (1-DNJ) and compare its effect with a combined treatment with ibuprofen. MPTP-treated mice were orally dosed with ibuprofen and/or 1-DNJ 1. Open-field test was used to evaluate behavioral changes. Immunohistochemistry for dopaminergic neurons marker (TH+) and microglia markers (Iba-1+; CD68+) were used to investigate neuronal integrity and microglial activation in the substantia nigra pars compacta (SNpc). The pro-inflammatory cytokines TNF-α and IL-6 were analysed by qPCR. Treatments with either 1-DNJ or Ibuprofen alone did not reduce the damage induced by MPTP intoxication. However, combined treatment with 1-DNJ and ibuprofen prevents loss of mesencephalic dopaminergic neurons, decreases the number of CD68+/ Iba-1+ cells, the microglia/neurons interactions, and the pro-inflammatory cytokines, and improves behavioral changes when compared with MPTP-treated animals. In conclusion, these data demonstrate that the combined treatment with a MMPs inhibitor (1-DNJ) plus an anti-inflammatory drug (ibuprofen) has neuroprotective effects open for future therapeutic interventions. Keywords Neuroinflammation . Microgliosis . Phagocytosis . Parkinson’s disease . Neurodegeneration
Introduction * SL Costa [email protected] * MT Herrero [email protected] 1
Clinical & Experimental Neuroscience (NiCE). Institute for Bio-Health Research of Murcia (IMIB), Institute for Aging Research (IUIE). School of Medicine, University of Murcia, Murcia, Spain
2
Department of Biochemistry and Biophysics, Laboratory of Neurochemistry and Cell Biology, Institute of Health Sciences, Federal University of Bahia, Salvador, Bahia 40110-100, Brazil
3
Department of Bioregulation, Laboratory of Neuroscience, Institute of Health Sciences, Federal University of Bahia, Salvador, Bahia 40110-100, Brazil
4
Faculty of Ceilandia, University of Brasilia – UnB, Brasilia, Federal District, Brazil
In the brain, continuous interactions between neurons, ext
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