当前位置： SCI文献检索 > Iranian Journal of Basic Medical Sciences期刊下所有文献 > Pharmacological evidence for lithium-induced neuroprotection against methamphetamine-induced neurodegeneration via Akt-1/GSK3 and CREB-BDNF signaling pathways.

Pharmacological evidence for lithium-induced neuroprotection against methamphetamine-induced neurodegeneration via Akt-1/GSK3 and CREB-BDNF signaling pathways.

Abstract：

Objectives:Neurodegeneration is an outcome of Methamphetamine (METH) abuse. Studies have emphasized on the neuroprotective properties of lithium. The current study is designed towards evaluating the role of Akt-1/GSK3 and CREB-BDNF signaling pathways in mediating lithium neuroprotection against METH-induced neurodegeneration in rats. Materials and Methods:Sixty adult male rats were randomly divided into five groups: control group (received 0.7 ml normal saline per rat for 28 days), METH group (given 10 mg/kg of METH intraperitoneally for 28 days), groups 3, 4, and 5 (given METH (10 mg/kg) and lithium (75, 150, and 300 mg/kg intraperitoneally, individually for 28 days). Morris water maze (MWM) was used to assess mental functions. In addition to hippocampal neurodegeneration, Brain-derived neurotrophic factor (BDNF), cAMP response element binding (CREB), Glycogen synthase kinase 3 (GSK3), and Protein kinase B (Akt-1) were assessed in isolated hippocampus. Results:METH abuse caused marked disorders in learning and memory that were dramatically improved with various doses of lithium. Furthermore, METH increased lipid peroxidation and the levels of oxidized form of interleukin 1 beta (IL-1β), glutathione (GSSG), Bax, tumor necrosis factor alpha (TNF-α), and GSK3, while attenuating the extent of glutathione (reduced form (GSH)), P-CREB, Bcl-2, BDNF, and Akt-1 in the hippocampus. Moreover, METH declined superoxide dismutase (SOD), glutathione reductase (GR), and glutathione peroxidase (GPx) activity in the hippocampus. Conversely, lithium attenuated METH-stimulated apoptosis, oxidative stress, and inflammation; while improving the extent of BDNF and P-CREB. Conclusion:Probably lithium possesses neuroprotection against METH-stimulated neurodegeneration in the hippocampus via Akt-1/GSK3β and CREB/BDNF signaling pathways.

journal_name

Iran J Basic Med Sci

journal_title

Iranian journal of basic medical sciences

authors

Mehrafza S,Kermanshahi S,Mostafidi S,Motaghinejad M,Motevalian M,Fatima S

doi

10.22038/ijbms.2019.30855.7442

subject

Has Abstract

pub_date

2019-08-01 00:00:00

pages

856-865

issue

eissn

2008-3866

issn

2008-3874

journal_volume

pub_type

杂志文章

在线工具

Pharmacological evidence for lithium-induced neuroprotection against methamphetamine-induced neurodegeneration via Akt-1/GSK3 and CREB-BDNF signaling pathways.