Article Information
Aritcle Type: Research Article
Citation: Li S, Tian S, Sun L, Liang Z, Cheng X, et al. (2015) Association of Cdk5 and Soluble Oligomeric Species of β-amyloid Induced Tau Hyperphosphorylation. J Neurol Neurobiol 1(3): doi http://dx.doi.org/10.16966/2379-7150.108
Copyright: © 2015 Li S, et al. This is an openaccess article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Publication history:
Authors :
Shanshan Li1# Sumin Tian2# Lingzhi Sun1 Zhihao Liang1 Xiaohui Cheng1 Han Wang1 Yuxin Ma1 Jing Liu1 Guoying Li1* Qing Mei Wang3
1Department of Anatomy and Histology, School of Basic Medicine, Guangdong Pharmaceutical University, Guangzhou, Guangdong, China
2Department of Physiology, School of Basic Medicine, Guangdong Pharmaceutical University, Guangzhou, Guangdong, China
3Department of Physical Medicine and Rehabilitation, Spaulding Rehabilitation Hospital, Boston, MA, USA#These authors contributed equally to this work.
*Corresponding author: Dr. Guoying Li, Department of Anatomy and Histology, Basic Medical College, Guangdong Pharmaceutical University, Guangzhou, Guangdong, 510006, China, Tel: +86-020-39352232; Fax:+86-020-39352186; E-mail: gzlgying820@sina.com
Alzheimer’s disease (AD) is a progressive neurodegenerative disease with deteriorating memory loss in the aged population. Currently, its exact pathogenesis remains elusive. Some studies have shown that soluble oligomeric Aβ (β-amyloid), inducing hyperphosphorylation of tau, may be the initial link to AD pathogenesis. However, it is poorly known how Aβ influences tau phosphorylation; Results, in this study, soluble oligomeric Aβ42 peptide was injected into the hippocampus of mice with saline as a control. Hematoxylin and eosin (HE) staining showed that Aβ42 was mainly deposited in the Cornu Ammonis area 1 (CA1). Within 7 to 21 days after the operation, the area of Aβ42 decreased gradually. Compared to the control, the expression of phosphorylated tau (p-tau) was significantly increased, suggesting that soluble Aβ oligomers activated phosphorylation of tau and increased total tau. Meanwhile, we found that elevated Cdk5, mainly in the CA1 area and subgranular zone (SGZ), correlates with increased phosphorylation of tau. Conclusions, thus, the results suggest that hyperphosphorylation of tau induced by soluble amyloid Aβ is associated with an increased level of Cdk5.
Alzheimer’s disease; β-amyloid; tau; Cdk5
Figure 1: Histological changes in the hippocampus. (A) HE staining in normal hippocampus of BALB/c mice. (C) HE staining in NS-injected hippocampus. (E) HE staining in Aβ42-injected hippocampus. (B, D, F), respectively, represent the region of high magnification in (A, C, E). (F) HE staining showed neuronal loss at the injection site surrounding Aβ peptide. Scale bar=200 μm in (A, C, E) and 50 μm in (B, D, F).
Figure 2: Immunostaining of Aβ in the hippocampus. (A) NS-injected group. (B, D), respectively, represent the region of high magnification in (A, C). (B) Higher magnification of negative Aβ aggregation at the injection site from NS-injected hippocampus. (C) Aβ42-injected group. (D) Aβ aggregation in SGZ of DG from Aβ42-injected hippocampus. Scale bar=200 μm in (A, C) and 100 μm in (B, D).
Figure 3: Immunofluorescence for expression of hyperphosphorylated tau in hippocampus. (A) Tau staining in control group (BALB / c + NS). (B, C) represent the region of high magnification in (A). (B) Negative au expression located in CA1. (C) Negative tau expression located in DG. (D) Tau staining in Aβ42-injected group (BALB / c + Aβ42). (E, F), respectively, represent the region of high magnification in (D). (E) p-tau located in CA1. (F) p-tau located in DG. Scale bar=100 μm in (A, D) and 50 μm in (B, C, E, F).
Figure 4: Immunofluorescence for expression of Cdk5 in the hippocampus. (A) Cdk5 staining in control group (BALB / c + NS). (B, C) represent the region of high magnification in (A). (B) Negative Cdk5 expression located in CA1. (C) Negative Cdk5 expression located in DG. (D) Cdk5 staining in Aβ42-injected group (BALB / c + Aβ42). (E, F), respectively, represent the region of high magnification in (D). (E) Cdk5 located in CA1. (F) Cdk5 located in DG. Scale bar=100 μm in (A, D) and 50 μm in (B, C, E, F).
Figure 5: Protein levels of tau and Cdk5 in hippocampus 7 days after Aβ42 injection. (A) Detection of protein levels of tau and Cdk5 using western blot. (B) Histograms represent the relative density of tau. Asterisks indicate data significantly different from those of NS injection (*P <0.01, student two-tailed t test). n=10 mice per group; error bars, SEM. (C) Histograms represent the relative density of Cdk5. Asterisks indicate data significantly different from those of NS injection (*P <0.01, student two-tailed t test). n=10 mice per group; error bars, SEM.
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Figure 2: Immunostaining of Aβ in the hippocampus. (A) NS-injected group. (B, D), respectively, represent the region of high magnification in (A, C). (B) Higher magnification of negative Aβ aggregation at the injection site from NS-injected hippocampus. (C) Aβ42-injected group. (D) Aβ aggregation in SGZ of DG from Aβ42-injected hippocampus. Scale bar=200 μm in (A, C) and 100 μm in (B, D).
Figure 3: Immunofluorescence for expression of hyperphosphorylated tau in hippocampus. (A) Tau staining in control group (BALB / c + NS). (B, C) represent the region of high magnification in (A). (B) Negative au expression located in CA1. (C) Negative tau expression located in DG. (D) Tau staining in Aβ42-injected group (BALB / c + Aβ42). (E, F), respectively, represent the region of high magnification in (D). (E) p-tau located in CA1. (F) p-tau located in DG. Scale bar=100 μm in (A, D) and 50 μm in (B, C, E, F).
Figure 4: Immunofluorescence for expression of Cdk5 in the hippocampus. (A) Cdk5 staining in control group (BALB / c + NS). (B, C) represent the region of high magnification in (A). (B) Negative Cdk5 expression located in CA1. (C) Negative Cdk5 expression located in DG. (D) Cdk5 staining in Aβ42-injected group (BALB / c + Aβ42). (E, F), respectively, represent the region of high magnification in (D). (E) Cdk5 located in CA1. (F) Cdk5 located in DG. Scale bar=100 μm in (A, D) and 50 μm in (B, C, E, F).
Figure 5: Protein levels of tau and Cdk5 in hippocampus 7 days after Aβ42 injection. (A) Detection of protein levels of tau and Cdk5 using western blot. (B) Histograms represent the relative density of tau. Asterisks indicate data significantly different from those of NS injection (*P <0.01, student two-tailed t test). n=10 mice per group; error bars, SEM. (C) Histograms represent the relative density of Cdk5. Asterisks indicate data significantly different from those of NS injection (*P <0.01, student two-tailed t test). n=10 mice per group; error bars, SEM.
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