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

Bita Soltanian,Nahid Masoudian,Gholam Hossein Riazi,Marzieh Dehghan Shasaltaneh

doi:10.1007/s11033-021-06629-x

Abstract

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. The groups in this study included Aβ (Group 1), METH (Group 2), Aβ + METH (METH after adding Aβ for 24h) (Group 3 as treated group), METH + Aβ (Aβ after adding METH for 24h) (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. 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.

Highlights

Alzheimer’s disease (AD) is the most frequent neurodegenerative condition which causes dementia in elderly people all over the planet [1, 2]
The expression of GSK3β, Cdk5, and PKCα genes decreased in the prevention group, while GSK3β and Cdk5 were amplified in the treatment group
The level of GSK3α and GSK3β proteins in the treatment group increased, while it decreased in the prevention group

Summary

Introduction

Alzheimer’s disease (AD) is the most frequent neurodegenerative condition which causes dementia in elderly people all over the planet [1, 2]. Astrocytes are the most abundant glial cells, as well as the scavenging cells in the brain They play a significant role in the pathogenesis of AD [5], the functions of which can influence neural survival. They can support neurons in many different ways including energy production of brain, ion, pH balance, synapse formation, remodeling, and oxidative stress regulation [6]. These glial cells participate in clearing Aβ in vitro and play a key role in the early stages of AD [7]. Since functional loss of astrocytes is associated with AD, we investigated the effects of low dose of methamphetamine (METH) on primary fetal human astrocytes under a stress paradigm as a possible model for AD

Methods

Results

Discussion

Conclusion