Abstract
BackgroundBrain aging is an important risk factor in many human diseases, such as Alzheimer’s disease (AD). The production of excess reactive oxygen species (ROS) mediated by nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2) and the maturation of inflammatory cytokines caused by activation of the NOD-like receptor protein 1 (NLRP1) inflammasome play central roles in promoting brain aging. However, it is still unclear when and how the neuroinflammation appears in the brain during aging process.MethodsIn this study, we observed the alterations of learning and memory impairments, neuronal damage, NLRP1 inflammasome activation, ROS production and NOX2 expression in the young 6-month-old (6 M) mice, presenile 16 M mice, and older 20 M and 24 M mice.ResultsThe results indicated that, compared to 6 M mice, the locomotor activity, learning and memory abilities were slightly decreased in 16 M mice, and were significantly decreased in 20 M and 24 M mice, especially in the 24 M mice. The pathological results also showed that there were no significant neuronal damages in 6 M and 16 M mice, while there were obvious neuronal damages in 20 M and 24 M mice, especially in the 24 M group. Consistent with the behavioral and histological changes in the older mice, the activity of β-galactosidase (β-gal), the levels of ROS and IL-1β, and the expressions of NLRP1, ASC, caspase-1, NOX2, p47phox and p22phox were significantly increased in the cortex and hippocampus in the older 20 M and 24 M mice.ConclusionOur study suggested that NLRP1 inflammasome activation may be closely involved in aging-related neuronal damage and may be an important target for preventing brain aging.
Highlights
Brain aging has been reported to be an important risk factor in many human diseases, such as Alzheimer’s disease (AD) and Parkinson’s disease (PD) [1]
The results showed that the mean moving distance (m) (Fig. 1A; F(3,41) = 7.698, P < 0.01), the mean moving speed (m/s) (Fig. 1B; F(3,41) = 7.685, P < 0.01), the number of line crossing (Fig. 1C; F(3,41) = 7.035, P < 0.01), and standing up (Fig. 1D, F(3,41) = 15.72, P < 0.01) had significant effects, and they were significantly decreased in 20 M and 24 M mice compared to 6 M mice
The moving distance and the mean moving speed were significantly decreased, while the number of lines crossing and number of standing were not significantly decreased in 16 M compared to 6 M mice
Summary
Brain aging has been reported to be an important risk factor in many human diseases, such as Alzheimer’s disease (AD) and Parkinson’s disease (PD) [1]. Sun et al Behavioral and Brain Functions (2021) 17:11 inflammation may be a "prodrome" to AD [4] It is still unclear when and how the neuroinflammation takes place during aging process. NLRP1 inflammasome activation in hippocampal neurons significantly exacerbates age-related cognitive impairment [10]. The production of excess reactive oxygen species (ROS) mediated by nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2) and the maturation of inflammatory cytokines caused by activation of the NOD-like receptor protein 1 (NLRP1) inflammasome play central roles in promoting brain aging. It is still unclear when and how the neuroinflammation appears in the brain during aging process
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