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    Downregulatory effect of miR-342-3p on epileptogenesis in the PTZ-kindling model
    (Springer, 2022) Pala, Mukaddes; Meral, Ismail; Acikgoz, Nilgun Pala; Yilmaz, Senay Gorucu; Okur, Semra Karaca; Acar, Seyma; Akbas, Fahri
    Background Epileptogenesis is a process that results in neurons firing abnormally, causing seizures. Increasing evidence has shown that miRNAs expressed in the epileptic hippocampus are involved in epileptogenesis. We demonstrated the expression changes of miRNAs that may be effective in epileptogenesis in silico analysis in the kindling model created with Pentylenetetrazole (PTZ). Thus, we aimed to identify the target genes responsible for epileptogenesis. Methods and results Fifteen male Wistar-albino rats (200-230 g) were randomly divided into two groups control (n = 6) and PTZ (n = 9). The control group received 0.5 ml saline, and the PTZ group (35 mg/kg i.p.) intraperitoneally (i.p.) (11 times, every other day) to induce tonic-clonic seizures. Seizures were observed and scored 30 min after PTZ injection. After the last dose of PTZ (75 mg/kg) administration, the hippocampus tissues of the rats were removed by anesthesia. Analysis of miRNAs was performed with the Affymetrix gene chip miRNA sequence (728 miRNA) and confirmed by the Real-Time Polymerase Chain Reaction (Real-Time PCR) method (29 miRNAs). We evaluated the expression change of the target gene of miRNA, whose expression change was detected using in silico analysis, by q-RT PCR. Eight miRNAs with changes in expression were detected. Of these miRNAs, miR-342-p was downregulated in the PTZ group and was statistically significant (p < 0.005). Ultimately, we determined that the target gene of miR-342-p is a metabotropic glutamate receptor 2 (GRM2) and that GRM2 expression is upregulated. Conclusions Downregulation of miR-342-3p in the PTZ kindling model may result in the upregulation of GRM2.
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    Evaluation of the Antioxidative and Protective Effects of Thymoquinone in a Pentylenetetrazole-induced Epilepsy Model
    (2025) Pala, Mukaddes; Meral, Ismail; acikgoz, nilgun; Hanikoglu, Ferhat; Kucukcetin, Ikbal Ozen; OZDEM, SEBAHAT; Yılmaz, Şenay Görücü
    Objective: Epilepsy is a common neurological disorder that leads to neuronal excitability and provokes various forms of cellular reorganization in the brain. We investigated the antioxidative and protective effects of thymoquinone (TQ) from the perspective of biomarkers in serum samples of rats using a pentylenetetrazol (PTZ)-induced epilepsy model. Methods: Twenty-one adult, male Wistar albino rats were randomly assigned to three groups. (1) Control (n=6); 0.5 mL saline (i.p.). (2) PTZ (n=7); 35 mg/kg PTZ (i.p.). (3) TQ+PTZ (n=8); 20 mg/kg TQ orally (p.o.)+ 35 mg/kg PTZ (i.p.). To induce kindling, PTZ was injected at a subconvulsive dose (35 mg/kg, i.p.) every other day for 24 days. Then, on the 26th day of the study, a single loading dose of PTZ (75 mg/kg) was injected into the animals. Seizure severity was evaluated with the Racine scale. Blood samples were taken from rats under anesthesia by the cardiac puncture method. The serum levels of myeloperoxidase (MPO), ischemia-modified albumin, total oxidant status (TOS), total antioxidant status (TAS), advanced oxidation protein products (AOPP), total sulfhydryl (T. sulfhydryl), and paraoxonase-1 (PON-1) were evaluated colorimetrically by the ELISA method, using a spectrophotometer. Results: A significant relationship was found between PTZ and TQ+PTZ groups for TAS (p=0.020), TOS (p=0.006), AOPP (p=0.015), and T. sulfhydryl (p=0.009). MPO and PON-1 were not significant (p>0.05). Conclusion: TQ may be used as an adjuvant agent in the regulation of epileptic seizures with its antioxidative and protective functions in the PTZ-induced epilepsy model. At the same time, serum parameters can potentially be diagnostic tools for the effective managing of treatment.
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    Thymoquinone ameliorates symptoms of Parkinson's disease in a 6-OHDA rat model by downregulation of miR-204-3p
    (Lippincott Williams & Wilkins, 2024) Pala, Mukaddes; Meral, Ismail; Acikgoz, Nilguen Pala; Mengi, Murat; Gokce, Meryem Betul Erdim; Unsal, Rumeysa; Yilmaz, Senay Gorucu
    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.