Abstract
Background: There is a significant gender difference in the incidence and symptoms of Alzheimer's disease (AD), but its mechanisms are not completely understood. Recent studies showed that NLRP1 inflammasome was overexpressed in females under some pathological conditions such as nodular melanoma. Whether NLRP1 signals have a gender difference in AD has not been elucidated. This study was designed to investigate gender difference on the expressions of NLRP1 signals including NLRP1, Capase-1 and IL-1β in the brains of APP/PS1+/− mice.Methods: Female and male APP/PS1+/− mice (30-weeks-old) were used in this study. Amyloid-β (Aβ) plaques were stained with Congo red dye and cell apoptosis was detected by TUNEL staining. Expressions of NLRP1, Capase-1 and IL-1β were measured by immunofluorescent staining and Western blotting assay.Results: The numbers of Aβ plaques in cortex and hippocampus and neuronal apoptosis in cortex were 4 and 2-folds in females than males, respectively (P < 0.001). The average size of Aβ plaques in both cortex (females: 3527.11 ± 539.88 μm2 vs. males: 1920.44 ± 638.49 μm2) and hippocampus (females: 1931 ± 308.61 μm2 vs. males: 1038.55 ± 220.40 μm2) were also larger in females than males (P < 0.01). More interestingly, expressions of NLRP1, Caspase-1, and IL-1β were markedly increased in the cortex of females as compared with males.Conclusions: These findings show that NLRP1 signals are higher in brains of female APP/PS1+/− mice than males, which may be related to the gender differences of AD.
Highlights
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that is characterized by symptoms like memory impairment, cognitive dysfunction, perception disturbance and language problems, and by neuropathological alterations including excess deposition of extracellular betaamyloid peptides (Aβ), aggregation and accumulation of intracellular hyperphosphorylated tau protein, and neuronal loss in some areas of the brain (Dos Santos Picanco et al, 2018; Veitch et al, 2019)
Congo red staining showed that the numbers of Aβ plaques were 4-folds higher in both cortex and hippocampus of female APP/PS1+/− mice than the otherwise identical male mice (P < 0.001)
The neuronal apoptosis was further confirmed by TUNEL (Figure 1E), which showed an increased 50.64% apoptotic cells in female APP/PS1+/− mice (P < 0.05) (Figure 1F)
Summary
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that is characterized by symptoms like memory impairment, cognitive dysfunction, perception disturbance and language problems, and by neuropathological alterations including excess deposition of extracellular betaamyloid peptides (Aβ), aggregation and accumulation of intracellular hyperphosphorylated tau protein, and neuronal loss in some areas of the brain (Dos Santos Picanco et al, 2018; Veitch et al, 2019). The recognition molecules of inflammasomes are classified into nucleotide-binding oligomerization domainlike receptors (NLR) and hemopoietic interferon-inducible nuclear receptors (HIN) (Schroder and Tschopp, 2010). Recent studies have shown that activation of NLRP inflammasomes is relevant to the pathogenesis of cardio-cerebrovascular diseases (Singhal et al, 2014; van Hout and Bosch, 2018). There is a significant gender difference in the incidence and symptoms of Alzheimer’s disease (AD), but its mechanisms are not completely understood. Recent studies showed that NLRP1 inflammasome was overexpressed in females under some pathological conditions such as nodular melanoma. Whether NLRP1 signals have a gender difference in AD has not been elucidated. This study was designed to investigate gender difference on the expressions of NLRP1 signals including NLRP1, Capase-1 and IL-1β in the brains of APP/PS1+/− mice
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