Alteration of gene expression in reactive astrocytes induced by Aβ1-42 using low dose of methamphetamine

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 A beta (Group 1), METH (Group 2), A beta + METH (METH after adding A beta for 24 h) (Group 3 as treated group), METH + A beta (A beta after adding METH for 24 h) (Group 4 as prevention group), and control group. Then, the gene expression of Bax, Bcl-X, PKC alpha, GSK3 beta, and Cdk5 was evaluated. In addition, phosphorylated tau, p-GSK3 beta, GSK3 beta, and GSK3 alpha 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 GSK3 beta, Cdk5, and PKC alpha genes decreased in the prevention group, while GSK3 beta and Cdk5 were amplified in the treatment group. Furthermore, the level of GSK3 alpha and GSK3 beta 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-3 beta and CdK-5, as well as enhanced activity of PKC alpha 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.

Automated summary

The low dose of METH may have a protective effect in preventing and treating AD, reducing the expression of GSK3 beta, Cdk5, and PKC alpha genes in the prevention group while increasing GSK3 beta and Cdk5 in the treatment group. Additionally, it can inhibit the phosphorylated tau protein and show improvements in cell apoptosis and cell cycle in both treatment and prevention groups.