Biomol Ther.  2018 Mar;26(2):115-120. 10.4062/biomolther.2016.248.

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

• Park JA
• Lee CH

• KMID: 2429050
• DOI: http://doi.org/10.4062/biomolther.2016.248

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.

Keyword

Duloxetine; Chronic cerebral hypoperfusion; Hippocamus; Neuroprotection; mTOR/p70S6K signaling pathway; Pro-inflammatory cytokines

MeSH Terms

Brain
CA1 Region, Hippocampal
Carotid Artery, Common
Cognition Disorders
Dementia, Vascular
Duloxetine Hydrochloride*
Models, Animal
Neurons*
Neuroprotection
Neuroprotective Agents*
Phosphorylation
Ribosomal Protein S6 Kinases, 70-kDa
Duloxetine Hydrochloride
Neuroprotective Agents
Ribosomal Protein S6 Kinases, 70-kDa