Role of Reelin signaling pathway in the pathogenesis of Alzheimer&rsquo;s disease model mice

YAN Ming-chao ZHAO Pei-wen CAO Jing-jing WANG Xiao-qing WANG Qian SUN Yi-zheng CHENG Yan-hong DENG Jin-bo*

doi:10.16098/j.issn.0529-1356.2016.06.001

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Acta Anatomica Sinica ›› 2016, Vol. 47 ›› Issue (6) : 721-730. DOI: 10.16098/j.issn.0529-1356.2016.06.001

Neurobiology

Role of Reelin signaling pathway in the pathogenesis of Alzheimer’s disease model mice

YAN Ming-chao ZHAO Pei-wen CAO Jing-jing WANG Xiao-qing WANG Qian SUN Yi-zheng CHENG Yan-hong DENG Jin-bo*

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Abstract

Objective To investigate the role of DNA methylation, Reelin and Notch pathways in the pathogenesis of Alzheimer’s disease(AD). Methods A total of 184 wild-type (WT) and AD mice were used for Golgi staining, immunofluorescent labeling, Western blotting and transmission electron microscopy in this study. Results The pathological changes occurred after postnatal 6 months (P6M) in the hippocampus and neocortex of AD mice, such as amyloid plaques and neurofibrillary tangles. Astrocytes and microglia usually were clustered around amyloid plaques in AD mice. With age increasing, Reelin accumulated around amyloid plaques and formed amyloid-like deposits. In AD mice, the expression of Notch1 receptor with both full-length Notch1 and Notch intracellular domain(NICD) decreased. DNA methylation decreased in AD hippocampus and neocortex; especially in amyloid plaques, the DNA methylation almost disappeared. For instance, the expression of Dnmt3a and Dnmt1 were decreased in AD mice. Conclusion The amyloid plaques in AD mice can induce the cluster of astrocytes and microglia and the accumulation of Reelin. The abnormal expressions of Notch1 receptor and DNA methyltransferase probably are the causes of the neural dysfunction in AD.

Key words

Alzheimer’s disease / Amyloid plaque / DNA methylation / Notch1 receptor / Reelin / Amyloid procursor protein/presenilin-1 double transgenic mouse

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YAN Ming-chao ZHAO Pei-wen CAO Jing-jing WANG Xiao-qing WANG Qian SUN Yi-zheng CHENG Yan-hong DENG Jin-bo. Role of Reelin signaling pathway in the pathogenesis of Alzheimer’s disease model mice[J]. Acta Anatomica Sinica. 2016, 47(6): 721-730 https://doi.org/10.16098/j.issn.0529-1356.2016.06.001

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