Aminochrome Induces Neuroinflammation and Dopaminergic Neuronal Loss: A New Preclinical Model to Find Anti-inflammatory and Neuroprotective Drugs for Parkinson's Disease.

التفاصيل البيبلوغرافية
العنوان:	Aminochrome Induces Neuroinflammation and Dopaminergic Neuronal Loss: A New Preclinical Model to Find Anti-inflammatory and Neuroprotective Drugs for Parkinson's Disease.
المؤلفون:	De Araújo FM; Laboratory of Neurochemistry and Cell Biology, Department of Biochemistry and Biophysics, Institute of Health Sciences, Federal University of Bahia, Salvador, Bahia, 40110-100, Brazil.; Clinical & Experimental Neuroscience (NiCE), Institute for Bio-Health Research of Murcia (IMIB), Institute for Aging Research (IUIE), School of Medicine, University of Murcia, Campus Mare Nostrum, Murcia, Spain., Frota AF; Laboratory of Neurochemistry and Cell Biology, Department of Biochemistry and Biophysics, Institute of Health Sciences, Federal University of Bahia, Salvador, Bahia, 40110-100, Brazil., de Jesus LB; Laboratory of Neurochemistry and Cell Biology, Department of Biochemistry and Biophysics, Institute of Health Sciences, Federal University of Bahia, Salvador, Bahia, 40110-100, Brazil., Macedo TC; Laboratory of Neurochemistry and Cell Biology, Department of Biochemistry and Biophysics, Institute of Health Sciences, Federal University of Bahia, Salvador, Bahia, 40110-100, Brazil., Cuenca-Bermejo L; Clinical & Experimental Neuroscience (NiCE), Institute for Bio-Health Research of Murcia (IMIB), Institute for Aging Research (IUIE), School of Medicine, University of Murcia, Campus Mare Nostrum, Murcia, Spain., Sanchez-Rodrigo C; Clinical & Experimental Neuroscience (NiCE), Institute for Bio-Health Research of Murcia (IMIB), Institute for Aging Research (IUIE), School of Medicine, University of Murcia, Campus Mare Nostrum, Murcia, Spain., Ferreira KMS; Laboratory of Neurochemistry and Cell Biology, Department of Biochemistry and Biophysics, Institute of Health Sciences, Federal University of Bahia, Salvador, Bahia, 40110-100, Brazil., de Oliveira JVR; Laboratory of Neurochemistry and Cell Biology, Department of Biochemistry and Biophysics, Institute of Health Sciences, Federal University of Bahia, Salvador, Bahia, 40110-100, Brazil., de Fatima Dias Costa M; Laboratory of Neurochemistry and Cell Biology, Department of Biochemistry and Biophysics, Institute of Health Sciences, Federal University of Bahia, Salvador, Bahia, 40110-100, Brazil., Segura-Aguilar J; Molecular & Clinical Pharmacology, ICBM, Faculty of Medicine, University of Chile, Independencia, 1027, Santiago, Chile., Costa SL; Laboratory of Neurochemistry and Cell Biology, Department of Biochemistry and Biophysics, Institute of Health Sciences, Federal University of Bahia, Salvador, Bahia, 40110-100, Brazil., Herrero MT; Clinical & Experimental Neuroscience (NiCE), Institute for Bio-Health Research of Murcia (IMIB), Institute for Aging Research (IUIE), School of Medicine, University of Murcia, Campus Mare Nostrum, Murcia, Spain. mtherrer@um.es., Silva VDA; Laboratory of Neurochemistry and Cell Biology, Department of Biochemistry and Biophysics, Institute of Health Sciences, Federal University of Bahia, Salvador, Bahia, 40110-100, Brazil. vdsilva@ufba.br.
المصدر:	Cellular and molecular neurobiology [Cell Mol Neurobiol] 2023 Jan; Vol. 43 (1), pp. 265-281. Date of Electronic Publication: 2022 Jan 06.
نوع المنشور:	Journal Article
اللغة:	English
بيانات الدورية:	Publisher: Kluwer Academic/Plenum Publishers Country of Publication: United States NLM ID: 8200709 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1573-6830 (Electronic) Linking ISSN: 02724340 NLM ISO Abbreviation: Cell Mol Neurobiol Subsets: MEDLINE
أسماء مطبوعة:	Publication: 1999- : New York : Kluwer Academic/Plenum Publishers Original Publication: New York : Plenum Press, c1981-
مواضيع طبية MeSH:	Parkinson Disease/metabolism , Neuroprotective Agents/pharmacology , Neuroprotective Agents/therapeutic use , Neuroprotective Agents/metabolism, Rats ; Male ; Animals ; Rats, Wistar ; Oxidopamine ; Neuroinflammatory Diseases ; Dopamine/metabolism ; Tumor Necrosis Factor-alpha/metabolism ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; Dopaminergic Neurons/metabolism ; Anti-Inflammatory Agents/pharmacology ; Anti-Inflammatory Agents/therapeutic use ; Anti-Inflammatory Agents/metabolism ; Disease Models, Animal ; Microglia/metabolism
مستخلص:	Studies have suggested aminochrome as an endogenous neurotoxin responsible for the dopaminergic neuron degeneration in Parkinson's disease (PD). However, neuroinflammation, an important alteration in PD pathogenesis, has been strictly induced in vitro by aminochrome. The aim of this study was to characterize the neuroinflammation induced in vivo by aminochrome. Wistar rats (male, 250-270 g) received a unilateral single dose by stereotaxic injection of saline into three sites in the striatum in the negative control group, or 32 nmol 6-hydroxydopamine (6-OHDA) in the positive control, or 6 nmol aminochrome. After 14 days, histological and molecular analyses were performed. We observed by immunofluorescence that aminochrome, as well as 6-OHDA, induced an increase in the number of Iba-1 ⁺ cells and in the number of activated (Iba-1 ⁺ / CD68 ⁺ ) microglia. An increase in the number of S100b ⁺ cells and in the GFAP expression were also evidenced in the striatum and the SNpc of animals from aminochrome and positive control group. Dopaminergic neuronal loss was marked by reduction of TH ⁺ cells and confirmed with reduction in the number of Nissl-stained neurons in the SNpc of rats from aminochrome and positive control groups. In addition, we observed by qPCR that aminocrhome induced an increase in the levels of IL-1β, TNF-α, NLRP3, CCL5 and CCR2 mRNA in the SNpc. This work provides the first evidence of microgliosis, astrogliosis and neuroinflammation induced by aminochrome in an in vivo model. Since aminochrome is an endogenous molecule derived from dopamine oxidation present in the targeted neurons in PD, these results reinforce the potential of aminochrome as a useful preclinical model to find anti-inflammatory and neuroprotective drugs for PD. Aminochrome induced dopaminergic neuronal loss, microglial activation, astroglial activation and neuroinflammation marked by an increase in NLRP3, IL1β, TNF-α, CCL2, CCL5 and CCR2. (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
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معلومات مُعتمدة:	PDSE -47/2017 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior; FPU 18/02549 Ministerio de Ciencia, Innovación y Universidades; FIS PI13 01293 Federación Española de Enfermedades de Parkinson; 19540/PI/14 Fundación Séneca; 429127/2018-9 Conselho Nacional de Desenvolvimento Científico e Tecnológico; Research Fellowship Conselho Nacional de Desenvolvimento Científico e Tecnológico
فهرسة مساهمة:	Keywords: Aminochrome; Animal model; Dopamine; Neuroinflammation; Parkinson’s disease
المشرفين على المادة:	39984-17-3 (aminochrome 1) 0 (Neuroprotective Agents) 8HW4YBZ748 (Oxidopamine) VTD58H1Z2X (Dopamine) 0 (Tumor Necrosis Factor-alpha) 0 (NLR Family, Pyrin Domain-Containing 3 Protein) 0 (Anti-Inflammatory Agents)
تواريخ الأحداث:	Date Created: 20220106 Date Completed: 20230106 Latest Revision: 20230111
رمز التحديث:	20240628
DOI:	10.1007/s10571-021-01173-5
PMID:	34988761
قاعدة البيانات:	MEDLINE

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تدمد:	1573-6830
DOI:	10.1007/s10571-021-01173-5