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

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.