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Nigrostriatal Inflammation Is Associated with Nonmotor Symptoms in an Experimental Model of Prodromal Parkinson's Disease.
Nigrostriatal Inflammation Is Associated with Nonmotor Symptoms in an Experimental Model of Prodromal Parkinson's Disease.
- Source :
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Neuroscience [Neuroscience] 2024 Jun 21; Vol. 549, pp. 65-75. Date of Electronic Publication: 2024 May 13. - Publication Year :
- 2024
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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.<br /> (Copyright © 2024 IBRO. Published by Elsevier Inc. All rights reserved.)
- 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
Subjects
Details
- Language :
- English
- ISSN :
- 1873-7544
- Volume :
- 549
- Database :
- MEDLINE
- Journal :
- Neuroscience
- Publication Type :
- Academic Journal
- Accession number :
- 38750924
- Full Text :
- https://doi.org/10.1016/j.neuroscience.2024.05.011