Pretreated duloxetine protects hippocampal CA1 pyramidal neurons from ischemia-reperfusion injury through decreases of glial activation and oxidative stress.

Abstract

Duloxetine (DXT), a serotonin/norepinephrine reuptake inhibitor, is widely used for the treatment of major depressive disorders. In the present study, we investigated the neuroprotective effect of pre-treated DXT in the hippocampal CA1 region following transient global cerebral ischemia. Pre-treatment with 40mg/kg DXT protected pyramidal neurons in the CA1 region from ischemia-reperfusion injury. In addition, pre-treatment with DXT reduced ischemia-induced activations of microglia and astrocytes in the ischemic CA1 region. On the other hand, we found that pre-treatment with DXT did not increase 4-hydroxy-2-noneal (a marker for lipid peroxidation) and significantly increased the expression of Cu, Zn-superoxide dismutase, an antioxidant, in the CA1 pyramidal neurons compared with non-treated those after ischemia-reperfusion. These results indicate that pre-treated DXT has neuroprotective effect against transient global cerebral ischemia and suggest that the neuroprotective effect of DXT may be due to the attenuation of ischemia-induced glial activation as well as the decrease of oxidative stress.

• Authors: Tae-Kyeong Lee, Joon Ha Park, Ji Hyeon Ahn, Myoung Cheol Shin, Jun Hwi Cho, Eun Joo Bae, Young-Myeong Kim, Moo-Ho Won, Choong-Hyun Lee
• Journal: Journal of the neurological sciences (J Neurol Sci) Vol. 370 Pg. 229-236 (Nov 15 2016) ISSN: 1878-5883 [Electronic] Netherlands
• PMID: 27772765 (Publication Type: Journal Article)
• Copyright: Copyright © 2016 Elsevier B.V. All rights reserved.

Chemical References

• Neuroprotective Agents
• Serotonin and Noradrenaline Reuptake Inhibitors
• Duloxetine Hydrochloride
• Superoxide Dismutase-1

Topics

• Animals
• Brain Ischemia (drug therapy, metabolism, pathology)
• CA1 Region, Hippocampal (drug effects, metabolism, pathology)
• Drug Evaluation, Preclinical
• Duloxetine Hydrochloride (pharmacology)
• Gerbillinae
• Male
• Neuroglia (drug effects, metabolism, pathology)
• Neuroprotective Agents (pharmacology)
• Oxidative Stress (drug effects, physiology)
• Pyramidal Cells (drug effects, metabolism, pathology)
• Reperfusion Injury (drug therapy, metabolism, pathology)
• Serotonin and Noradrenaline Reuptake Inhibitors (pharmacology)
• Superoxide Dismutase-1 (metabolism)