PROJECT TYPE: 1002-Fast Support
PROJECT NUMBER: 219S253
SUMMARY:
Background and Purpose: Parkinson's disease (PD) is characterized by motor and non-motor symptoms associated with dopaminergic and non-dopaminergic injury. Vortioxetine is a multimodal serotonergic antidepressant with potential procognitive effects. This study aimed to explore the effects of vortioxetine on motor functions, spatial learning and memory, and depression-like behavior in the rotenone-induced rat model of PD.
Method: Male Sprague-Dawley rats were daily administered with the rotenone (2 mg/kg, s.c.) and/or vortioxetine (10 mg/kg, s.c.) for 28 days. Motor functions (rotarod, catalepsy, open-field), depression-like behaviors (sucrose preference test), anxiety (elevated plus maze), and spatial learning and memory abilities (novel object recognition and Morris water maze) were evaluated in behavioral tests. Then, immunohistochemical (TH, α-synuclein, pS129-α-synuclein, cleaved caspase-3, TLR-2), neurochemical (dopamine, noradrenaline, serotonin, glutamine, L-glutamic acid) and biochemical (TNF-α, IL-1ß, IL-6, NFΚBp65) analyzes were performed in the striatum, prefrontal cortex and hippocampus tissues.
Results: Vortioxetine treatment markedly reduced rotenone-induced neurodegeneration, improved motor and cognitive dysfunction, decreased depression-like behaviors without affecting anxiety-like parameters. Vortioxetine also restored the impaired inflammatory response and affected neurotransmitter levels in brain tissues. Interestingly, vortioxetine was thought to trigger a sort of dysfunction in basal ganglia as evidenced by increased Toll-like receptor-2 (TLR-2) and decreased TH immunoreactivity only in substantia nigra tissue of PD rats compared to the control group.
Conclusions: The present study indicates that vortioxetine has beneficial effects on motor dysfunction as well as cognitive impairment associated with neurodegeneration in the rotenone-induced PD model. Possible mechanisms underlying these beneficial effects cover TLR-2 inhibition and neurochemical restoration of vortioxetine.
01/12/2019 → 01/12/2020