Research Paper|Volume 10, Issue 12|pp 4188—4196

Fluoxetine-mediated inhibition of endoplasmic reticulum stress is involved in the neuroprotective effects of Parkinson’s disease

Tao Peng¹, Xiaoyan Liu¹, Jingtao Wang¹, Yu Liu¹, Zhenqiang FU¹, Xingrong Ma¹, Junmin Li¹, Guifang Sun¹, Yangfei Ji¹, Jingjing Lu¹, Wencui Wan², Hong Lu¹

¹Key-Disciplines Laboratory Clinical Medicine Henan, Department of Neurology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China
²Department of Ophthalmology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China

Received: September 10, 2018Accepted: December 6, 2018Published: December 24, 2018

https://doi.org/10.18632/aging.101716

Copyright: © 2018 Peng et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Background: Accumulating evidence suggests that Fluoxetine (FLX), an anti-depressant drug, has broad neurobiological functions and neuroprotective effects in central nervous system injury, but its roles in Parkinson's disease (PD) remain unclear. In this study, we aimed to evaluate whether fluoxetine attenuates rotenone-induced neurodegeneration in PD.

Methods: Male Sprague-Dawley rats were randomly allocated to control, rotenone-treated, rotenone + FLX-treated and FLX-treated groups. Behavioral tests including open field behavioral test and catalepsy measurement were taken to evaluate neurological behavioral measurements. Apoptosis was detected by TUNEL assay. Endoplasmic reticulum (ER)-related gene expressions were detected by qRT-PCR and western blot. Immunohistochemistry was performed to assess dopaminergic neuronal degeneration.

Results: We demonstrated that pretreatment with FLX (10.0 mg/kg, i.p.) significantly ameliorated the catalepsy symptom and increased locomotor activity. In addition, FLX markedly reversed the loss of dopaminergic neurons and suppressed the X‑box‑binding protein 1 (XBP1)/caspase-3-activated ER stress. Furthermore, FLX inhibited rotenone-mediated neurodegeneration through caspase-3-mediated neuronal apoptosis.

Conclusion: Taken together, our findings indicate that FLX has beneficial neuroprotective effects in PD and FLX might be a potential therapeutic agent for the treatment of PD. In light of its favorable properties, FLX should be evaluated in the treatment of PD as well as related neurologic disorders.