Thymoquinone ameliorates symptoms of Parkinson’s disease in a 6-OHDA rat model by downregulation of miR-204-3p

Author:

Pala Mukaddes1,Meral Ismail2,Pala Acikgoz Nilgün3,Mengi Murat4,Erdim Gokce Meryem Betül5,Unsal Rumeysa6,Polat Yalcin7,Akbas Fahri8,Gorucu Yilmaz Senay9

Affiliation:

1. Department of Physiology, Faculty of Medicine, Malatya Turgut Ozal University, Malatya

2. Department of Physiology, School of Medicine

3. Department of Neurology, Faculty of Medicine, Bezmialem Vakif University, Istanbul

4. Department of Physiology, Faculty of Medicine, Namik Kemal University, Tekirdag

5. Gynecology and Obstetrics, Umraniye Training and Research Hospital

6. Bakirkoy Prof. Dr. Mazhar Osman Mental Health and Nervous Diseases Training and Research Hospital

7. Department of Pathology, Faculty of Medicine, Biruni University

8. Department of Medical Biology, Faculty of Medicine, Bezmialem Vakif University, Istanbul

9. Department of Nutrition and Dietetics, Faculty of Health Science, Gaziantep University, Gaziantep, Turkey

Abstract

microRNAs (miRNAs) play a significant role in the pathophysiology of Parkinson’s disease. In this study, we evaluated the neuroprotective effect of thymoquinone on the expression profiles of miRNA and cognitive functions in the 6-hydroxydopamine (6-OHDA)-induced Parkinson’s model. Male adult Wistar albino rats (200–230 g, n = 36) were randomly assigned to six groups: Sham, thymoquinone (10 mg/kg, p.o.), 6-OHDA, 6-OHDA + thymoquinone (10 mg/kg), 6-OHDA + thymoquinone (20 mg/kg), and 6-OHDA + thymoquinone (50 mg/kg). Behavioral changes were detected using the open field and the elevated plus maze tests. The mature 728 miRNA expressions were evaluated by miRNA microarray (GeneChip miRNA 4.0). Ten miRNAs were selected (rno-miR-212-5p, rno-miR-146b-5p, rno-miR-150-5p, rno-miR-29b-2-5p, rno-miR-126a-3p, rno-miR-187-3p, rno-miR-34a-5p, rno-miR-181d-5p, rno-miR-204-3p, and rno-miR-30c-2-3p) and confirmed by real-time PCR. Striatum samples were stained with hematoxylin-eosin to determine the effect of dopaminergic lesions. One-way ANOVA test and independent sample t-test were used for statistical analyses. rno-miR-204-3p was upregulated at 6-OHDA and downregulated at the 50 mg/kg dose of thymoquinone. In conclusion, thymoquinone at a dose of 50 mg/kg ameliorates symptoms of Parkinson’s disease in a 6-OHDA rat model by downregulation of miR-204-3p. Also, the results showed that thymoquinone can improve locomotor activity and willing exploration and decreased anxiety. Therefore, thymoquinone can be used as a therapeutic agent.

Publisher

Ovid Technologies (Wolters Kluwer Health)

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