Duloxetine by modulating the Akt/GSK3 signaling pathways has neuroprotective effects against methamphetamine-induced neurodegeneration and cognition impairment in rats

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. © 2019, Shiraz University of Medical Sciences. All rights reserved

Landscape evolution and agro-sylvo-pastoral activities on the Gorgan Plain (NE Iran)in the last 6000 years

The Gorgan Plain (NE Iran) is characterized by fertile soils formed on a loess plateau and is at present primarily exploited for intensive agriculture. However, the timing and intensity of the human impact on the landscape in the past are still unclear. A sediment core, taken from the centre of the eastern Gorgan Plain in the Kongor Lake covering the major part of the Holocene from 6.1 to 0.8 ka (all ages are calibrated before present), has been studied for pollen, non-pollen palynomorphs, botanical macroremains, insects, charcoal, geochemistry, biomarkers and magnetism in order to provide new insights into the evolution of the landscape and to estimate the intensity of human activities. The data obtained suggest a dry period between 5.9 and 3.9 ka and an increase in regional humidity afterwards with a maximum between 2.7 and 0.7 ka, during the period of the Persian empires (Achaemenid through Sasanian) and the Islamic era. The eastern part of the Gorgan Plain was characterized by open steppe landscapes during the last 6 ka, which most likely were used for pasture and at least since 2.7 ka for agriculture including arboriculture. The strongest anthropogenic impact on the environment around the Kongor site is documented during the Parthian and Sasanian Empires (200 BC–651 AD) and the Islamic era up to the eve of the Mongol invasion