1. Nigrostriatal Inflammation Is Associated with Nonmotor Symptoms in an Experimental Model of Prodromal Parkinson's Disease.
- Author
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Oliveira BDS, Toscano ECB, Abreu LKS, Fernandes HB, Amorim RF, Ferreira RN, Machado CA, Carvalho BC, da Silva MCM, de Oliveira ACP, Rachid MA, Rocha NP, Teixeira AL, da Silva ER, and de Miranda AS
- Subjects
- Animals, Male, Dopaminergic Neurons pathology, Dopaminergic Neurons metabolism, Dopaminergic Neurons drug effects, Neuroinflammatory Diseases pathology, Corpus Striatum metabolism, Corpus Striatum drug effects, Corpus Striatum pathology, Mice, Microglia metabolism, Microglia pathology, Inflammation chemically induced, Inflammation metabolism, Inflammation pathology, Brain-Derived Neurotrophic Factor metabolism, Anxiety etiology, 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine pharmacology, Substantia Nigra metabolism, Substantia Nigra pathology, Substantia Nigra drug effects, Disease Models, Animal, Mice, Inbred C57BL, Prodromal Symptoms
- Abstract
Recent evidence has supported a pathogenic role for neuroinflammation in Parkinson's disease (PD). Inflammatory response has been associated with symptoms and subtypes of PD. However, it is unclear whether immune changes are involved in the initial pathogenesis of PD, leading to the non-motor symptoms (NMS) observed in its prodromal stage. The current study aimed to characterize the behavioral and cognitive changes in a toxin-induced model of prodromal PD-like syndrome. We also sought to investigate the role of neuroinflammation in prodromal PD-related NMS. Male mice were subjected to bilateral intranasal infusion with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or saline (control group), followed by comprehensive behavioral, pathological and neurochemical analysis. Intranasal MPTP infusion was able to cause the loss of dopaminergic neurons in the substantia nigra (SN). In parallel, it induced impairment in olfactory discrimination and social memory consolidation, compulsive and anxiety-like behaviors, but did not influence motor performance. Iba-1 and GFAP expressions were increased in the SN, suggesting an activated state of microglia and astrocytes. Consistent with this, MPTP mice had increased levels of IL-10 and IL-17A, and decreased levels of BDNF and TrkA mRNA in the SN. The striatum showed increased IL-17A, BDNF, and NFG levels compared to control mice. In conclusion, neuroinflammation may play an important role in the early stage of experimental PD-like syndrome, leading to cognitive and behavioral changes. Our results also indicate that intranasal administration of MPTP may represent a valuable mouse model for prodromal PD., (Copyright © 2024 IBRO. Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
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