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1.
Neuroscience ; 549: 65-75, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38750924

RESUMO

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.


Assuntos
Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Sintomas Prodrômicos , Substância Negra , Animais , Masculino , Substância Negra/metabolismo , Substância Negra/patologia , Substância Negra/efeitos dos fármacos , Neurônios Dopaminérgicos/patologia , Neurônios Dopaminérgicos/metabolismo , Neurônios Dopaminérgicos/efeitos dos fármacos , Doenças Neuroinflamatórias/patologia , Corpo Estriado/metabolismo , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/patologia , Camundongos , Microglia/metabolismo , Microglia/patologia , Inflamação/induzido quimicamente , Inflamação/metabolismo , Inflamação/patologia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Ansiedade/etiologia , 1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina/farmacologia
2.
J Neuroimmunol ; 385: 578242, 2023 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-37951202

RESUMO

The pathophysiology of post-traumatic brain injury (TBI) behavioral and cognitive changes is not fully understood, especially in its mild presentation. We designed a weight drop TBI model in mice to investigate the role of neuroinflammation in behavioral and cognitive sequelae following mild TBI. C57BL/6 mice displayed depressive-like behavior at 72 h after mild TBI compared with controls, as indicated by a decrease in the latency to first immobility and climbing time in the forced swim test. Additionally, anxiety-like behavior and hippocampal-associated spatial learning and memory impairment were found in the elevated plus maze and in the Barnes maze, respectively. Levels of a set of inflammatory mediators and neurotrophic factors were analyzed at 6 h, 24 h, 72 h, and 30 days after injury in ipsilateral and contralateral hemispheres of the prefrontal cortex and hippocampus. Principal components analysis revealed two principal components (PC), which represented 59.1% of data variability. PC1 (cytokines and chemokines) expression varied between both hemispheres, while PC2 (neurotrophic factors) expression varied only across the investigated brain areas. Our model reproduces mild TBI-associated clinical signs and pathological features and might be a valuable tool to broaden the knowledge regarding mild TBI pathophysiology as well as to test potential therapeutic targets.


Assuntos
Concussão Encefálica , Lesões Encefálicas Traumáticas , Camundongos , Animais , Concussão Encefálica/complicações , Camundongos Endogâmicos C57BL , Encéfalo/patologia , Lesões Encefálicas Traumáticas/complicações , Fatores de Crescimento Neural , Cognição , Aprendizagem em Labirinto/fisiologia , Modelos Animais de Doenças
3.
J Neuroimmunol ; 330: 5-11, 2019 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-30763800

RESUMO

Several studies have proposed cerebral malaria (CM) as a CD4+ and CD8+ T lymphocyte-mediated disease. However, there are no data regarding the recruitment and/or persistence of these cells in the CNS following the phase of infection resolution. Glutamate-mediate excitotoxicity has also been implicated in CM. Blockade of glutamate NMDA receptors by its noncompetitive antagonist MK801 modulates cytokine and neurotrophic factors expression preventing cognitive and depressive-like behavior in experimental CM. Herein, we aim to investigate the role of T lymphocytes in later outcomes in CM, and whether the protective role of MK801 is associated with T lymphocytes response.


Assuntos
Malária Cerebral/tratamento farmacológico , Malária Cerebral/imunologia , Plasmodium berghei/efeitos dos fármacos , Plasmodium berghei/imunologia , Linfócitos T/imunologia , Animais , Maleato de Dizocilpina/farmacologia , Maleato de Dizocilpina/uso terapêutico , Antagonistas de Aminoácidos Excitatórios/farmacologia , Antagonistas de Aminoácidos Excitatórios/uso terapêutico , Feminino , Camundongos , Camundongos Endogâmicos C57BL , Linfócitos T/efeitos dos fármacos , Resultado do Tratamento
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