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http://dx.doi.org/10.4062/biomolther.2016.248

Neuroprotective Effect of Duloxetine on Chronic Cerebral Hypoperfusion-Induced Hippocampal Neuronal Damage  

Park, Jin-A (Department of Pharmacy, College of Pharmacy, Dankook University)
Lee, Choong-Hyun (Department of Pharmacy, College of Pharmacy, Dankook University)
Publication Information
Biomolecules & Therapeutics / v.26, no.2, 2018 , pp. 115-120 More about this Journal
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 $TNF-{\alpha}$ and $IL-1{\beta}$ 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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