Bita Soltanian1, Marzieh Dehghan Shasaltaneh2, Gholam Hossein Riazi3, Nahid Masoudian1. 1. Department of Biology, College of Science, Damghan Branch, Islamic Azad University, Damghan, Iran. 2. Department of Biology, Faculty of Science, University of Zanjan, Zanjan, Iran. dehghan@znu.ac.ir. 3. Laboratory of Neuro-Organic Chemistry, Institute of Biochemistry and Biophysics (IBB), University of Tehran, Tehran, Iran.
Abstract
BACKGROUND: Alzheimer's disease (AD) is a degenerative brain disorder. Due to the relationship between the functional loss of astrocytes and AD, the present study aims to evaluate the effects of the low dose of methamphetamine (METH) on primary fetal human astrocytes under a stress paradigm as a possible model for AD. METHODS AND RESULTS: The groups in this study included Aβ (Group 1), METH (Group 2), Aβ + METH (METH after adding Aβ for 24 h) (Group 3 as treated group), METH + Aβ (Aβ after adding METH for 24 h) (Group 4 as prevention group), and control group. Then, the gene expression of Bax, Bcl-X, PKCα, GSK3β, and Cdk5 was evaluated. In addition, phosphorylated tau, p-GSK3β, GSK3β, and GSK3α proteins were assessed by western blotting. Further, cell cycle arrest and apoptosis were checked by flow cytometry and Hoechst staining. Based on the results, the expression of GSK3β, Cdk5, and PKCα genes decreased in the prevention group, while GSK3β and Cdk5 were amplified in the treatment group. Furthermore, the level of GSK3α and GSK3β proteins in the treatment group increased, while it decreased in the prevention group. Additionally, a decrease occurred in the percentage of necrosis and early apoptosis in the treatment and prevention groups. The results of the cell cycle indicated that G1 increased, while G2 decreased in the prevention group. CONCLUSION: The pure form of METH can prevent from activating GSK-3β and CdK-5, as well as enhanced activity of PKCα to inhibit phosphorylated tau protein. Therefore, a low dose of METH may have a protective effect or reducing role in the pathway of tau production in reactive astrocytes.
BACKGROUND: Alzheimer's disease (AD) is a degenerative brain disorder. Due to the relationship between the functional loss of astrocytes and AD, the present study aims to evaluate the effects of the low dose of methamphetamine (METH) on primary fetal human astrocytes under a stress paradigm as a possible model for AD. METHODS AND RESULTS: The groups in this study included Aβ (Group 1), METH (Group 2), Aβ + METH (METH after adding Aβ for 24 h) (Group 3 as treated group), METH + Aβ (Aβ after adding METH for 24 h) (Group 4 as prevention group), and control group. Then, the gene expression of Bax, Bcl-X, PKCα, GSK3β, and Cdk5 was evaluated. In addition, phosphorylated tau, p-GSK3β, GSK3β, and GSK3α proteins were assessed by western blotting. Further, cell cycle arrest and apoptosis were checked by flow cytometry and Hoechst staining. Based on the results, the expression of GSK3β, Cdk5, and PKCα genes decreased in the prevention group, while GSK3β and Cdk5 were amplified in the treatment group. Furthermore, the level of GSK3α and GSK3β proteins in the treatment group increased, while it decreased in the prevention group. Additionally, a decrease occurred in the percentage of necrosis and early apoptosis in the treatment and prevention groups. The results of the cell cycle indicated that G1 increased, while G2 decreased in the prevention group. CONCLUSION: The pure form of METH can prevent from activating GSK-3β and CdK-5, as well as enhanced activity of PKCα to inhibit phosphorylated tau protein. Therefore, a low dose of METH may have a protective effect or reducing role in the pathway of tau production in reactive astrocytes.
Authors: Michelle G Tan; Wei-Ting Chua; Margaret M Esiri; A David Smith; Harry V Vinters; Mitchell K Lai Journal: J Neurosci Res Date: 2010-05-01 Impact factor: 4.164
Authors: John F Castro-Alvarez; S Alejandro Uribe-Arias; Kenneth S Kosik; Gloria P Cardona-Gómez Journal: Front Aging Neurosci Date: 2014-09-10 Impact factor: 5.750