Duloxetine by Modulating the Akt/GSK3 Signaling Pathways Has Neuroprotective Effects against Methamphetamine-Induced Neurodegeneration and Cognition Impairment in Rats
Journal Title: Iranian Journal of Medical Sciences - Year 2019, Vol 44, Issue 2
Abstract
Background: The neuroprotective effects of duloxetine, as an antidepressant agent, and the neurodegenerative effects of methamphetamine have been shown in previous studies. Nonetheless, their exact neurochemical and behavioral effects are still unclear. In the current study, we sought to clarify the molecular mechanisms involved in the protective effects of duloxetine against methamphetamine-induced neurodegeneration. Methods: Forty adult male rats were divided randomly into 5 groups. Group 1 was the negative control and received normal saline, Group 2 was the positive control and received methamphetamine, and Groups 3, 4, and 5 were concurrently treated with methamphetamine (10 mg/kg) and duloxetine (5, 10, and 15 mg/kg, respectively). All the treatments were continued for 21 days. Between days 17 and 21, the Morris Water Maze (MWM) was used to assess learning and memory in the treated groups. On day 22, the hippocampus was isolated from each rat and oxidative, antioxidant, and inflammatory factors were measured. Additionally, the expression levels of the total and phosphorylated forms of the Akt and GSK3 proteins were evaluated via the ELISA method. Results: Duloxetine in all the administered doses ameliorated the effects of the methamphetamine-induced cognition impairment in the MWM. The chronic abuse of methamphetamine increased malondialdehyde, tumor necrosis factor-α, and interleukin-1β, while it decreased superoxide dismutase, glutathione peroxidase, and glutathione reductase activities. Duloxetine not only prevented these malicious effects of methamphetamine but also activated the expression of Akt (both forms) and inhibited the expression of GSK3 (both forms) in the methamphetamine-treated rats. Conclusion: We conclude that the Akt/GSK3 signaling pathways might have a critical role in the protective effects of duloxetine against methamphetamine-induced neurodegeneration and cognition impairment.
Authors and Affiliations
Mehrasa Rahimi Borumand, Majid Motaghinejad, Manijeh Motevalian, Mina Gholami
Keywords
Related Articles
- EP ID EP478440
- DOI -
- Views 117
- Downloads 0
Assessment of Subclinical Myocardial Changes in Non-Alcoholic Fatty Liver Disease: A Case-Control Study Using Speckle Tracking Echocardiography
Background: Considering the association between cardiac abnormalities and non-alcoholic fatty liver disease (NAFLD), the present study aimed to evaluate the relationship between biopsy-proven NAFLD and functional echocar...
Juglans Regia L. Leaf Extract Attenuates Diabetic Nephropathy Progression in Experimental Diabetes: An Immunohistochemical Study
Background: There is accumulating evidence that Juglans regia L. (GRL) leaf extract has hypoglycemic and antioxidative properties. The present study aimed to investigate the protective effects of GRL leaf extract against...
Anticonvulsant Activity of Viola tricolor against Seizures Induced by Pentylenetetrazol and Maximal Electroshock in Mice
Background: Recently, there has been much more interest in the use of medicinal plants in search of novel therapies for human neurodegenerative diseases such as epilepsy. In the present study, we investigated the anticon...
Primary Leiomyosarcoma of the Mesentery: A Case Report
Mesenteric masses are infrequent lesions ranging from benign cysts to aggressive malignancies and often present a diagnostic and therapeutic challenge. The mesentery is a frequent recipient of metastases from the gastroi...
First Report of the Isolation of Nocardiathailandicafrom the Bronchoalveolar Lavage of a Patient in Iran
Nocardiae are Gram-positive, filamentous, aerobic, relatively slow-growing, and weakly acid-fast bacteria which cause nocardiosis in humans. We describe a 53-year-old patient with chronic bronchitis referred to Al-Zahra...