Spatial Training Ameliorates Long-Term Alzheimer's Disease-Like Pathological Deficits by Reducing NLRP3 Inflammasomes in PR5 Mice.
Neurotherapeutics
; 16(2): 450-464, 2019 04.
Article
em En
| MEDLINE
| ID: mdl-30560481
ABSTRACT
Recent studies have suggested that cognitive training could delay memory loss in Alzheimer's disease (AD). However, whether and how cognitive training produces long-term benefits remains unclear. Here, 10-month-old PR5 mice were spatially trained in a water maze for 4 consecutive weeks. The novel object recognition test (NORT), Western blots, Golgi staining, and ELISA were used to examine behavioral, biochemical, and pathological measures immediately after training and 3 months later. Immediately after training, we found that spatial training significantly improved cognitive performance; reduced tau neuropathology; increased the expression level of synaptophysin, PSD93, and PSD95 in the hippocampus; and increased the number of dendritic spines in PR5 mice. The expression levels of NLRP3, caspase-1, and interleukin (IL)-1ß, which were significantly elevated in PR5 mice, were reversed by spatial training. Interestingly, these effects persisted 3 months later. To further detect the role of NLRP3 in spatial training, PR5/NLRP3-/- mice and PR5/NLRP3+/- mice were also used in our study. PR5/NLRP3-/- mice showed better cognitive performance than PR5 mice. After 1 week of spatial training, these changes (including those in expression levels of synaptophysin, PSD93, and PSD95; the number of dendritic spines; and caspase-1 and IL-1ß content in PR5 mice) could be totally reversed in PR5/NLRP3-/- and PR5/NLRP3+/- mice. In addition, there was a positive correlation between NLRP3 content and the expression levels of caspase-1 and IL-1ß. These results show an important role for the NLRP3/caspase-1/IL-1ß axis in ameliorating the effect of spatial training on cognitive impairment in PR5 mice.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Cognição
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Espinhas Dendríticas
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Inflamassomos
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Doença de Alzheimer
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Aprendizagem Espacial
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Proteína 3 que Contém Domínio de Pirina da Família NLR
Limite:
Animals
Idioma:
En
Revista:
Neurotherapeutics
Assunto da revista:
NEUROLOGIA
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
China