Nigrostriatal Inflammation Is Associated with Nonmotor Symptoms in an Experimental Model of Prodromal Parkinson’s Disease

• Published in: Neuroscience Vol. 549; pp. 65 - 75
• Main Authors: Oliveira, Bruna da Silva, Toscano, Eliana Cristina de Brito, Abreu, Larissa Katharina Sabino, Fernandes, Heliana de Barros, Amorim, Renan Florindo, Ferreira, Rodrigo Novaes, Machado, Caroline Amaral, Carvalho, Brener Cunha, da Silva, Maria Carolina Machado, de Oliveira, Antônio Carlos Pinheiro, Rachid, Milene Alvarenga, Rocha, Natália Pessoa, Teixeira, Antônio Lúcio, da Silva, Elizabeth Ribeiro, de Miranda, Aline Silva
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 21-06-2024
• Subjects: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine - pharmacology; Animals; Anxiety - etiology; Brain-Derived Neurotrophic Factor - metabolism; Corpus Striatum - drug effects; Corpus Striatum - metabolism; Corpus Striatum - pathology; Disease Models, Animal; Dopaminergic Neurons - drug effects; Dopaminergic Neurons - metabolism; Dopaminergic Neurons - pathology; Inflammation - chemically induced; Inflammation - metabolism; Inflammation - pathology; Male; Mice; Mice, Inbred C57BL; Microglia - metabolism; Microglia - pathology; MPTP model; neuroinflammation; Neuroinflammatory Diseases - pathology; nonmotor symptoms; PD-like syndrome; Prodromal Symptoms; Substantia Nigra - drug effects; Substantia Nigra - metabolism; Substantia Nigra - pathology; PD-like syndrome; IFN-γ; BBB; PD; TNF-α; neuroinflammation; nonmotor symptoms; NMS; MPTP model; IL-1β; IL-6
• ISSN: 0306-4522; 1873-7544; 1873-7544
• DOI: 10.1016/j.neuroscience.2024.05.011

Illustration summarizing the major findings of the current work.
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•Intranasal MPTP infusion is a suitable model for prodromal PD.•MPTP mice display olfactory discrimination and social memory impairment.•MPTP mice present compulsive and anxiety-like behaviors.•Intranasal MPTP infusion induces enhanced levels of IL-17A in the SNpc.•Intranasal MPTP infusion induces decreased levels of BDNF in the SNpc.
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.