Trehalose Neuroprotective Effects on the Substantia Nigra Dopaminergic Cells by Activating Autophagy and Non-canonical Nrf2 Pathways

Authors

  • Ali Noori-Zadeh Department of Clinical Biochemistry, Faculty of Allied Medical Sciences, Ilam University of Medical Sciences, Ilam, Iran.
  • Farzad Rajaei Cellular and Molecular Research Center, Qazvin University of Medical Sciences, Qazvin, Iran.
  • Hojjat-Allah Abbaszadeh Hearing Disorders Research Center, Loghman Hakim Medical Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. | Department of Anatomical Sciences and Biology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
  • Salar Bakhtiyari Department of Clinical Biochemistry, Faculty of Medicine, Ilam University of Medical Sciences, Ilam, Iran.
  • Shahram Darabi Cellular and Molecular Research Center, Qazvin University of Medical Sciences, Qazvin, Iran.
Abstract:

Trehalose, as a natural disaccharide, is known as an autophagy inducer. The neuroprotectiveeffects of trehalose in the rat model of Parkinson′s disease were the aim of the present study.Parkinson′s disease model was induced by injecting 6-hydroxydopamine (6-OHDA) in thestriatum of male Wistar rats. Apomorphine-induced behavior and substantia nigra neuronalcounts were applied to evaluate the neuroprotective effects of trehalose. The autophagy wasstudied using the expression of p62 and LC3II/LC3I ratio. In addition, the antioxidant effectsof trehalose were assessed by analyzing the levels of nuclear factor (erythroid-derived 2)-like2 (Nrf2) and also glutathione reductase (GR), glutathione peroxidase (GPx) and Catalase(CAT) enzymes. Moreover, the levels of 3, 4-dihydroxyphenylacetic acid (DOPAC) anddopamine (DA) were assessed.The behavioral test showed that trehalose in the treatment groupreduced the damage to the substantial nigra dopaminergic neurons, which was characterizedby improved motor and reduced rotations in the treatment group as compared with the lesiongroup. In the histological examinations of the treatment group, trehalose prevented thedestruction of dopaminergic neurons. Trehalose treatments increased autophagy (high LC3II/LC3I ratio) and the expression of the p62 protein as well. Through p62-dependent manner,it led to increased nuclear translocation of Nrf2 transcription factor and elevated expressionof downstream antioxidant enzymes, such as GR, GPx, and CAT, restoring DA and DOPACcontents of the cells. In the current study, trehalose simultaneously protects substantia nigradopaminergic cells by activating both non-canonical p62/SQSTM1-Keap1-Nrf2 and autophagypathways.

Upgrade to premium to download articles

Sign up to access the full text

Already have an account?login

similar resources

Neuroprotective Effect of Exogenous Melatonin on Dopaminergic Neurons of the Substantia Nigra in Ovariectomized Rats

Background: Melatonin has receptors in substantia nigra pars compacta (SNc) and regulates development of dopaminergic (DA) neurons. This study was undertaken to determine ability of melatonin to protect SNc dopaminergic neuron loss induced by estrogen deficiency in ovariectomized rats. Methods: Female rats were randomized into four groups of seven each: control, ethanol sham, ovariectomy (ovx) ...

full text

neuroprotective effect of exogenous melatonin on dopaminergic neurons of the substantia nigra in ovariectomized rats

background: melatonin has receptors in substantia nigra pars compacta (snc) and regulates development of dopaminergic (da) neurons. this study was undertaken to determine ability of melatonin to protect snc dopaminergic neuron loss induced by estrogen deficiency in ovariectomized rats. methods: female rats were randomized into four groups of seven each: control, ethanol sham, ovariectomy (ovx) ...

full text

Neuroprotective effect of exogenous melatonin on dopaminergic neurons of the substantia nigra in ovariectomized rats.

BACKGROUND Melatonin has receptors in substantia nigra pars compacta (SNc) and regulates development of dopaminergic (DA) neurons. This study was undertaken to determine ability of melatonin to protect SNc dopaminergic neuron loss induced by estrogen deficiency in ovariectomized rats. METHODS Female rats were randomized into four groups of seven each: control, ethanol sham, ovariectomy (ovx) ...

full text

Trehalose protects against oxidative stress by regulating the Keap1–Nrf2 and autophagy pathways

Dysfunction of autophagy, which regulates cellular homeostasis by degrading organelles and proteins, is associated with pathogenesis of various diseases such as cancer, neurodegeneration and metabolic disease. Trehalose, a naturally occurring nontoxic disaccharide found in plants, insects, microorganisms and invertebrates, but not in mammals, was reported to function as a mechanistic target of ...

full text

Antioxidant Role of Oleuropein on Midbrain and Dopaminergic Neurons of Substantia Nigra in Aged Rats

Background: Oleuropein is a phenolic compound which is present in the olive leaf extract. The purpose of the present study was to investigate the neuroprotective effect of oleuropein as an antioxidant agent on the substantia nigra in aged rats. Methods: Twenty 18-month-old Wistar rats (450-550 g) were randomly divided into control and experimental groups. The experimental group received a daily...

full text

My Resources

Save resource for easier access later

Save to my library Already added to my library

{@ msg_add @}


Journal title

volume 18  issue 3

pages  1419- 1428

publication date 2019-07-01

By following a journal you will be notified via email when a new issue of this journal is published.

Hosted on Doprax cloud platform doprax.com

copyright © 2015-2023