Biomolecules & Therapeutics  
Neuroprotective Effect of Duloxetine on Chronic Cerebral Hypoperfusion-Induced Hippocampal Neuronal Damage
Jin-A Park and Choong-Hyun Lee*
Department of Pharmacy, College of Pharmacy, Dankook University, Cheonan 31116, Republic of Korea
E-mail: anaphy@dankook.ac.kr
Tel: +82-41-550-1441, Fax: +82-41-559-7899
Received: November 1, 2016; Revised: December 19, 2016; Accepted: January 9, 2017; Published online: April 6, 2017.
© The Korean Society of Applied Pharmacology. All rights reserved.

Abstract
Chronic cerebral hypoperfusion (CCH), which is associated with onset of vascular dementia, causes cognitive impairment and neuropathological alterations in the brain. In the present study, we examined the neuroprotective effect of duloxetine (DXT), a potent and balanced serotonin/norepinephrine reuptake inhibitor, on CCH-induced neuronal damage in the hippocampal CA1 region using a rat model of permanent bilateral common carotid arteries occlusion. We found that treatment with 20 mg/kg DXT could attenuate the neuronal damage, the reduction of phosphorylations of mTOR and p70S6K as well as the elevations of TNF-α and IL- 1β levels in the hippocampal CA1 region at 28 days following CCH. These results indicate that DXT displays the neuroprotective effect against CCH-induced hippocampal neuronal death, and that neuroprotective effect of DXT may be closely related with the attenuations of CCH-induced decrease of mTOR/p70S6K signaling pathway as well as CCH-induced neuroinflammatory process.
Keywords: Duloxetine, Chronic cerebral hypoperfusion, Hippocamus, Neuroprotection, mTOR/p70S6K signaling pathway, Pro-inflammatory cytokines


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