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Öğe Deep phenotyping of miRNAs in exercise-induced cardiac hypertrophy and fibrosis(Indian Acad Sciences, 2023) Pala, Mukaddes; Yilmaz, Senay Gorucu; Altan, Mehmet; Sonmez, Osman Fuat; Dincer, Sensu; Mengi, Murat; Karabulut, AydinCardiac hypertrophy (CH) is an adaptational enlargement of the myocardium, in exposure to altered stress conditions or in case of injury which can lead to heart failure and death. MicroRNAs (miRNAs) are non-coding RNAs that play a significant role in modulating gene expression. Here, we aimed to identify new miRNAs effective in an experimental CH model and to find an epigenetic biomarker that could demonstrate therapeutic targets responsible for the pathology of heart tissue and serum. In this study, Sprague-Dawley male rats were divided into the training group (TG, n=9) and the control group (CG, n=6). Systolic and diastolic dimensions of the left ventricle and myocardial wall thickness were measured by echocardiography to assess CH. After the exercise program of the rats, miRNA expression measurements and histological analyses were performed. The 25,000 genes in the rat genome were searched using microarray analysis. A total of 128 miRNAs were selected according to the fold change rates, and nine miRNAs were validated for expression analysis. The terminal deoxynucleotidyl transferase dUTP nick (TUNEL) method was used to detect apoptotic cells. Cell proliferation was evaluated by the proliferative cell nuclear antigen (PCNA) method. Necrosis, bleeding, and intercellular edema were detected in TG. The mean histopathological score was higher in TG (p=0.03). There were rarely positive cells for apoptosis of both groups in cardiomyocytes. In the receiver characteristic curve analysis (ROC), the heart tissue rno-miR-290 had an area under the curve (AUC) of 0.920 with 100% sensitivity and 89.90% specificity (p=0.045), rno-miR-194-5p had AUC of 0.940 with 83.33% sensitivity and 100% specificity (p=0.003), and the serum rno-miR-132-3p AUC was 0.880 with 66.67% sensitivity and 100% specificity (p=0.004) in TG. miR-194-5p was used as a therapeutic target for remodeling the cardiac process. While miR-290 contributes to CH as a negative regulator, miR-132 in serum is effective in the pathological and physiological cardiac remodeling process and is a candidate biomarker.Öğe 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; Polat, YalcinBackground 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.Öğe Pentylenetetrazole-induced kindling rat model: miR-182 and miR-27b-3p mediated neuroprotective effect of thymoquinone in the hippocampus(Taylor & Francis Ltd, 2022) Pala, Mukaddes; Meral, Ismail; Acikgoz, Nilgun Pala; Yilmaz, Senay Gorucu; Taslidere, Elif; Okur, Sema Karaca; Acar, SeymaObjectives: Epilepsy is a neurological disease that pathologically affects brain functions. The epileptic hippocampus has modified microRNA(miRNA) levels. Therefore, we aimed to evaluate the neuroprotective effect of thymoquinone (TQ) in PTZ-induced epilepsy and to demonstrate the overlap between miRNA and mRNA expression profiles. Methods: Male adult Wistar albino rats (200-230 g, n = 20) were divided into three groups as control (n = 6), PTZ (n = 7), and TQ + PTZ (n = 7). The PTZ kindling model was created by injecting PTZ in sub convulsive doses to rats on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, and 24 of the study into animals. Clonic and tonic seizures were induced by injecting a convulsive dose of PTZ on day 26 of the study. Rats in the TQ+PTZ group were treated by oral gavage with a 20 mg/kg TQ 2 h before each PTZ injection. The rats in the control group were treated with 0.5 ml saline. Seizure severity was evaluated with the Racine scale. The genes and signaling pathways targeted by miRNAs were determined by bioinformatics analysis. Results: In the rat hippocampus, mature 728 miRNAs were analyzed by microarray and the nine miRNA were verified by quantitative Real-Time PCR. rno-miR-182 and rno-miR-27b-3p were up-regulated in the PTZ group and down-regulated in the TQ + PTZ group. Discussion: In the PTZ kindling epilepsy model, the expression of these two miRNAs was regulated by TQ and exerted a neuroprotective effect by controlling the activities of target genes.
