TY - JOUR ID - 13235 TI - Pharmacological evidence for lithium-induced neuroprotection against methamphetamine-induced neurodegeneration via Akt-1/GSK3 and CREB-BDNF signaling pathways JO - Iranian Journal of Basic Medical Sciences JA - IJBMS LA - en SN - 2008-3866 AU - Mehrafza, Shafagh AU - Kermanshai, Sareh AU - Mostafidi, Shahnaz AU - Motaghinejad, Majid AU - Motevalian, Manijeh AU - Fatima, Sulail AD - Department of pharmaceutical chemistry, faculty of pharmaceutical chemistry, pharmaceutical sciences branch, Islamic Azad University (IUAPS), Tehran, Iran AD - Research Center for Addiction and Risky Behaviors (ReCARB), Iran Psychiatric Center, Iran University of Medical Sciences, Tehran, Iran AD - Department of Pharmacology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran AD - Department of Physiology, Tehran University of Medical Sciences-International Campus (TUMS-IC), Tehran, Iran Y1 - 2019 PY - 2019 VL - 22 IS - 8 SP - 856 EP - 865 KW - Akt KW - BDNF KW - CREB KW - Lithium KW - Methamphetamine KW - GSK3 DO - 10.22038/ijbms.2019.30855.7442 N2 - 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. UR - https://ijbms.mums.ac.ir/article_13235.html L1 - https://ijbms.mums.ac.ir/article_13235_879af5783039013a2cbc3b40dc57e1ad.pdf ER -