دورية أكاديمية
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Neuroinflammation in early, late and recovery stages in a progressive parkinsonism model in rats.

التفاصيل البيبلوغرافية
العنوان: Neuroinflammation in early, late and recovery stages in a progressive parkinsonism model in rats.
المؤلفون: Cunha DMG; Behavioral Neuroscience Laboratory, Department of Pharmacology, Universidade Federal de São Paulo, São Paulo, Brazil., Becegato M; Behavioral Neuroscience Laboratory, Department of Pharmacology, Universidade Federal de São Paulo, São Paulo, Brazil., Meurer YSR; Behavioral Neuroscience Laboratory, Department of Pharmacology, Universidade Federal de São Paulo, São Paulo, Brazil., Lima AC; Behavioral Neuroscience Laboratory, Department of Pharmacology, Universidade Federal de São Paulo, São Paulo, Brazil., Gonçalves N; Behavioral Neuroscience Laboratory, Department of Pharmacology, Universidade Federal de São Paulo, São Paulo, Brazil., Bioni VS; Behavioral Neuroscience Laboratory, Department of Pharmacology, Universidade Federal de São Paulo, São Paulo, Brazil., Engi SA; Behavioral Neuroscience Laboratory, Department of Pharmacology, Universidade Federal de São Paulo, São Paulo, Brazil., Bianchi PC; Behavioral Neuroscience Laboratory, Department of Pharmacology, Universidade Federal de São Paulo, São Paulo, Brazil., Cruz FC; Behavioral Neuroscience Laboratory, Department of Pharmacology, Universidade Federal de São Paulo, São Paulo, Brazil., Santos JR; Behavioral and Evolutionary Neurobiology Laboratory, Department of Bioscience, Universidade Federal do Sergipe, Itabaiana, Brazil., Silva RH; Behavioral Neuroscience Laboratory, Department of Pharmacology, Universidade Federal de São Paulo, São Paulo, Brazil.
المصدر: Frontiers in neuroscience [Front Neurosci] 2022 Aug 26; Vol. 16, pp. 923957. Date of Electronic Publication: 2022 Aug 26 (Print Publication: 2022).
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Frontiers Research Foundation Country of Publication: Switzerland NLM ID: 101478481 Publication Model: eCollection Cited Medium: Print ISSN: 1662-4548 (Print) Linking ISSN: 1662453X NLM ISO Abbreviation: Front Neurosci Subsets: PubMed not MEDLINE
أسماء مطبوعة: Original Publication: Lausanne : Frontiers Research Foundation
مستخلص: Parkinson's disease (PD) is characterized by motor and non-motor signs, which are accompanied by progressive degeneration of dopaminergic neurons in the substantia nigra. Although the exact causes are unknown, evidence links this neuronal loss with neuroinflammation and oxidative stress. Repeated treatment with a low dose of reserpine-inhibitor of VMAT2-has been proposed as a progressive pharmacological model of PD. The aim of this study was to investigate whether this model replicates the neuroinflammation characteristic of this disease. Six-month-old Wistar rats received repeated subcutaneous injections of reserpine (0.1 mg/kg) or vehicle on alternate days. Animals were euthanized after 5, 10, or 15 injections, or 20 days after the 15th injection. Catalepsy tests (motor assessment) were conducted across treatment. Brains were collected at the end of each treatment period for immunohistochemical and RT-PCR analyzes. Reserpine induced a significant progressive increase in catalepsy duration. We also found decreased immunostaining for tyrosine hydroxylase (TH) in the substantia nigra pars compacta (SNpc) and increased GFAP + cells in the SNpc and dorsal striatum after 10 and 15 reserpine injections. Phenotyping microglial M1 and M2 markers showed increased number of CD11b + cells and percentage of CD11b + /iNOS + cells in reserpine-treated animals after 15 injections, which is compatible with tissue damage and production of cytotoxic factors. In addition, increased CD11b + /ArgI + cells were found 20 days after the last reserpine injection, together with an increment in IL-10 gene expression in the dorsal striatum, which is indicative of tissue repair or regeneration. Reserpine also induced increases in striatal interleukin TNF-alpha mRNA levels in early stages. In view of these results, we conclude that reserpine-induced progressive parkinsonism model leads to neuroinflammation in regions involved in the pathophysiology of PD, which is reversed 20 days after the last injection. These findings reveal that withdrawal period, together with the shift of microglial phenotypes from the pro-inflammatory to the anti-inflammatory stage, may be important for the study of the mechanisms involved in reversing this condition, with potential clinical applicability.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2022 Cunha, Becegato, Meurer, Lima, Gonçalves, Bioni, Engi, Bianchi, Cruz, Santos and Silva.)
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فهرسة مساهمة: Keywords: catalepsy; interleukins; microglia phenotypes; rats; reserpine; tyrosine hydroxylase
تواريخ الأحداث: Date Created: 20220912 Latest Revision: 20220913
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC9459164
DOI: 10.3389/fnins.2022.923957
PMID: 36090265
قاعدة البيانات: MEDLINE
الوصف
تدمد:1662-4548
DOI:10.3389/fnins.2022.923957