Selegiline acts as neuroprotective agent against methamphetamine-prompted mood and cognitive related behavior and neurotoxicity in rats: Involvement of CREB/BDNF and Akt/GSK3 signal pathways
<em><strong>Objective(s):</strong></em> Present study investigated the neuroprotective effects of selegiline and the molecular mechanisms involved in methamphetamine-induced neurotoxicity.<br /><em><strong>Materials and Methods:</strong></em> Mal...
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doaj-f7166f5363f5411aa30d653a934b9d3b2020-11-25T03:23:46ZengMashhad University of Medical SciencesIranian Journal of Basic Medical Sciences 2008-38662008-38742020-05-0123560661510.22038/ijbms.2020.38827.922114687Selegiline acts as neuroprotective agent against methamphetamine-prompted mood and cognitive related behavior and neurotoxicity in rats: Involvement of CREB/BDNF and Akt/GSK3 signal pathwaysSaba Feizipour0Sarvenaz Sobhani1Shafagh Mehrafza2Mina Gholami3Majid Motaghinejad4Manijeh Motevalian5Sepideh Safari6Reza Davoudizadeh7Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Chemistry, Pharmaceutical Sciences Branch, Islamic Azad University (IUAPS), Tehran, IranRazi Drug Research Center, Iran University of Medical Sciences, Tehran, IranDepartment of Pharmaceutical Chemistry, Faculty of Pharmaceutical Chemistry, Pharmaceutical Sciences Branch, Islamic Azad University (IUAPS), Tehran, IranDepartment of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, IranRazi Drug Research Center, Iran University of Medical Sciences, Tehran, Iran|Department of medicine, Qom branch, Islamic Azad University, IranDepartment of medicine, Qom branch, Islamic Azad University, IranRazi Drug Research Center, Iran University of Medical Sciences, Tehran, IranDepartment of medicine, Qom branch, Islamic Azad University, Iran<em><strong>Objective(s):</strong></em> Present study investigated the neuroprotective effects of selegiline and the molecular mechanisms involved in methamphetamine-induced neurotoxicity.<br /><em><strong>Materials and Methods:</strong></em> Male wistar rats were randomly divided into six groups (10 rats in each group). Group 1 and group 2 received normal saline and methamphetamine (10 mg/kg), respectively. Groups 3, 4, 5 and 6 were treated simultaneously with methamphetamine and selegiline. From day 22 to day 28, forced swim test, elevated plus maze, and open field test were conducted to assess mood (anxiety and depression) levels, and from day 17 to day 21, Morris Water Maze was conducted for cognition assessment. On day 29, hippocampus of the animals were isolated and evaluated by ELISA method for oxidative, antioxidant, and inflammatory factors and expression levels of active (total) and inactive (phosphorylated) forms of cyclic AMP response element binding protein (CREB), brain-derived neurotrophic factor (BDNF), Akt (Protein Kinase B) and glycogen synthase kinase 3 (GSK3) proteins. <br /><em><strong>Results:</strong></em> Selegiline reduced behavioral impacts caused by methamphetamine in all doses. Methamphetamine administration may improve malondialdehyde, tumor necrosis factor-alpha, interleukin-1 beta and GSK3 (both forms). Moreover, methamphetamine reduced the activity of superoxide dismutase, glutathione peroxidase, glutathione reductase, amount of BDNF, CREB and Akt (both forms).<br /><em><strong>Conclusion:</strong></em> Current research showed that selegiline can protect the brain from methamphetamine-prompted neurodegeneration, and this could be intervened by CREB -BDNF or Akt-GSK3 signaling pathways.http://ijbms.mums.ac.ir/article_14687_4390c00de09e9097e969d34364b73d0a.pdfanxietydepressionmethamphetamineneurotoxicityselegiline |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Saba Feizipour Sarvenaz Sobhani Shafagh Mehrafza Mina Gholami Majid Motaghinejad Manijeh Motevalian Sepideh Safari Reza Davoudizadeh |
spellingShingle |
Saba Feizipour Sarvenaz Sobhani Shafagh Mehrafza Mina Gholami Majid Motaghinejad Manijeh Motevalian Sepideh Safari Reza Davoudizadeh Selegiline acts as neuroprotective agent against methamphetamine-prompted mood and cognitive related behavior and neurotoxicity in rats: Involvement of CREB/BDNF and Akt/GSK3 signal pathways Iranian Journal of Basic Medical Sciences anxiety depression methamphetamine neurotoxicity selegiline |
author_facet |
Saba Feizipour Sarvenaz Sobhani Shafagh Mehrafza Mina Gholami Majid Motaghinejad Manijeh Motevalian Sepideh Safari Reza Davoudizadeh |
author_sort |
Saba Feizipour |
title |
Selegiline acts as neuroprotective agent against methamphetamine-prompted mood and cognitive related behavior and neurotoxicity in rats: Involvement of CREB/BDNF and Akt/GSK3 signal pathways |
title_short |
Selegiline acts as neuroprotective agent against methamphetamine-prompted mood and cognitive related behavior and neurotoxicity in rats: Involvement of CREB/BDNF and Akt/GSK3 signal pathways |
title_full |
Selegiline acts as neuroprotective agent against methamphetamine-prompted mood and cognitive related behavior and neurotoxicity in rats: Involvement of CREB/BDNF and Akt/GSK3 signal pathways |
title_fullStr |
Selegiline acts as neuroprotective agent against methamphetamine-prompted mood and cognitive related behavior and neurotoxicity in rats: Involvement of CREB/BDNF and Akt/GSK3 signal pathways |
title_full_unstemmed |
Selegiline acts as neuroprotective agent against methamphetamine-prompted mood and cognitive related behavior and neurotoxicity in rats: Involvement of CREB/BDNF and Akt/GSK3 signal pathways |
title_sort |
selegiline acts as neuroprotective agent against methamphetamine-prompted mood and cognitive related behavior and neurotoxicity in rats: involvement of creb/bdnf and akt/gsk3 signal pathways |
publisher |
Mashhad University of Medical Sciences |
series |
Iranian Journal of Basic Medical Sciences |
issn |
2008-3866 2008-3874 |
publishDate |
2020-05-01 |
description |
<em><strong>Objective(s):</strong></em> Present study investigated the neuroprotective effects of selegiline and the molecular mechanisms involved in methamphetamine-induced neurotoxicity.<br /><em><strong>Materials and Methods:</strong></em> Male wistar rats were randomly divided into six groups (10 rats in each group). Group 1 and group 2 received normal saline and methamphetamine (10 mg/kg), respectively. Groups 3, 4, 5 and 6 were treated simultaneously with methamphetamine and selegiline. From day 22 to day 28, forced swim test, elevated plus maze, and open field test were conducted to assess mood (anxiety and depression) levels, and from day 17 to day 21, Morris Water Maze was conducted for cognition assessment. On day 29, hippocampus of the animals were isolated and evaluated by ELISA method for oxidative, antioxidant, and inflammatory factors and expression levels of active (total) and inactive (phosphorylated) forms of cyclic AMP response element binding protein (CREB), brain-derived neurotrophic factor (BDNF), Akt (Protein Kinase B) and glycogen synthase kinase 3 (GSK3) proteins. <br /><em><strong>Results:</strong></em> Selegiline reduced behavioral impacts caused by methamphetamine in all doses. Methamphetamine administration may improve malondialdehyde, tumor necrosis factor-alpha, interleukin-1 beta and GSK3 (both forms). Moreover, methamphetamine reduced the activity of superoxide dismutase, glutathione peroxidase, glutathione reductase, amount of BDNF, CREB and Akt (both forms).<br /><em><strong>Conclusion:</strong></em> Current research showed that selegiline can protect the brain from methamphetamine-prompted neurodegeneration, and this could be intervened by CREB -BDNF or Akt-GSK3 signaling pathways. |
topic |
anxiety depression methamphetamine neurotoxicity selegiline |
url |
http://ijbms.mums.ac.ir/article_14687_4390c00de09e9097e969d34364b73d0a.pdf |
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