摘要
Background： Amyloid β （Aβ） has been established as a key factor for the pathological changes in the brains of patients with Alzheimer＇s disease （AD）, and cellular senescence is closely associated with aging and cognitive impairment. However, it remains blurred whether, in theAD brains, Aβ accelerates the neuronal senescence and whether this senescence, in turn, impairs the cognitive function. This study aimed to explore the expression of senescence-associated genes in the hippocampal tissue from young to aged 5XFAD mice and their age-matched wild type （WT） mice to determine whether senescent neurons are present in the transgenic AD mouse model. Methods： The 5XFAD mice and age-matched wild type mice, both raised from 1 to 18 months, were enrolled in the study. The senescence-associated genes in the hippocampus were analyzed and differentially expressed genes （DEGs） were screened by quantitative real-time polymerase chain reaction. Cognitive perfom3ance of the mice was evaluated by Y-maze and Morris water maze tests. Oligomeric Aβ（oAβ） （1-42） was applied to culture primary neurons to simulate the in vivo manifestation. Aging-related proteins were detected by Western blotting analysis and immunofluorescence. Results： In 5XFAD mice, of all the DEGs, the senescence-associated marker p16 was most significantly increased, even at the early age. It was mainly localized in neurons, with a marginal expression in astrocytes （labeled as glutamine synthetase）, nil expression in activated microglia （labeled as lba1）, and negatively correlated with the spatial cognitive impairments of 5XFAD mice. oAβ （1-42） induced the production of senescence-related protein p1 6, but not p53 in vitro, which was in line with the in vivo manifestation. Conclusions： oAβ-accelerated neuronal senescence may be associated with the cognitive impairment in 5XFAD mice. Senescence-associated marker p16 can serve as an indicator to estimate the cognitive prognosis for A D population.
Background： Amyloid β （Aβ） has been established as a key factor for the pathological changes in the brains of patients with Alzheimer＇s disease （AD）, and cellular senescence is closely associated with aging and cognitive impairment. However, it remains blurred whether, in theAD brains, Aβ accelerates the neuronal senescence and whether this senescence, in turn, impairs the cognitive function. This study aimed to explore the expression of senescence-associated genes in the hippocampal tissue from young to aged 5XFAD mice and their age-matched wild type （WT） mice to determine whether senescent neurons are present in the transgenic AD mouse model. Methods： The 5XFAD mice and age-matched wild type mice, both raised from 1 to 18 months, were enrolled in the study. The senescence-associated genes in the hippocampus were analyzed and differentially expressed genes （DEGs） were screened by quantitative real-time polymerase chain reaction. Cognitive perfom3ance of the mice was evaluated by Y-maze and Morris water maze tests. Oligomeric Aβ（oAβ） （1-42） was applied to culture primary neurons to simulate the in vivo manifestation. Aging-related proteins were detected by Western blotting analysis and immunofluorescence. Results： In 5XFAD mice, of all the DEGs, the senescence-associated marker p16 was most significantly increased, even at the early age. It was mainly localized in neurons, with a marginal expression in astrocytes （labeled as glutamine synthetase）, nil expression in activated microglia （labeled as lba1）, and negatively correlated with the spatial cognitive impairments of 5XFAD mice. oAβ （1-42） induced the production of senescence-related protein p1 6, but not p53 in vitro, which was in line with the in vivo manifestation. Conclusions： oAβ-accelerated neuronal senescence may be associated with the cognitive impairment in 5XFAD mice. Senescence-associated marker p16 can serve as an indicator to estimate the cognitive prognosis for A D population.
基金
We would like to thank teacher Hong-Zhi Huang from College of Foreign Languages of Fujian Medical University for the kindly help of text modifications and retouching of this paper. This study was supported by grants from National Natural Science Fotmdation of China （No. 81200991 and No. 81571257）, Fujian Provincial Natural Science Foundation （No. 2015J01398）, Fujian Provincial New Century Excellent Talents Support Program, China （JA13131）, and Young and Middle-aged Talent Training Key Project in Health System of Fujian Province （2014-ZQN-ZD- 11）.
