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Pharmacological Evidence for Lithium-Induced Neuroprotection Against Methamphetamine-Induced Neurodegeneration Via Akt- 1/Gsk3 and Creb-Bdnf Signaling Pathways Publisher



Mehrafza S1 ; Kermanshahi S1 ; Mostafidi S1 ; Motaghinejad M2 ; Motevalian M3 ; Fatima S4
Authors
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Authors Affiliations
  1. 1. Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Chemistry, Pharmaceutical Sciences Branch, Islamic Azad University (IUAPS), Tehran, Iran
  2. 2. Research Center for Addiction and Risky Behaviors (ReCARB), Iran Psychiatric Center, Iran University of Medical Sciences, Tehran, Iran
  3. 3. Department of Pharmacology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
  4. 4. Department of Physiology, Tehran University of Medical Sciences-International Campus (TUMS-IC), Tehran, Iran

Source: Iranian Journal of Basic Medical Sciences Published:2019


Abstract

Objective(s): 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. © 2019 Iranian Journal of Basic Medical Sciences. All rights reserved.
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