Selected microRNAs regulated during epileptogenesis and epilepsy in a rat model of temporal lobe epilepsy

• Autorzy: Bot A. , Debski K. , Lukasiuk K.
• Języki publikacji: EN

Abstrakty

EN

BACKGROUND AND AIMS: To verify expression level of selected microRNAs regulated during epileptogenesis and epilepsy in a rat model of temporal lobe epilepsy according to global analysis of miRNA expression and to characterize their cellular localization. METHODS: Epilepsy was induced by status epilepticus triggered by electrical stimulation of the lateral nucleus of the amygdala. Animals were video-EEG monitored to detect spontaneous seizures. Rats were sacrificed at 7, 14, 30 and 90 days after stimulation. The expression levels of selected miRNAs were verified using qPCR and cellular localization was determined using in situ hybridization combined with immunohistochemistry. Bioinformatics analysis was performed using R packages and Ingenuity Pathway Analysis Software. RESULTS: We have previously shown alterations in miRNA expression in the epileptic dentate gyrus. For qPCR analysis we selected 6 candidates and confirmed upregulation of miR-21, miR-132, miR-212, miR-370 and downregulation of miR-187 and miR-551b. At 90 days after stimulation, number and frequency of spontaneous seizures was positively correlated with expression level of upregulated miRNAs and negatively correlated with downregulated miRNAs. Hierarchical clustering of Spearman correlation between selected miRNAs and their target mRNAs expression levels revealed distinctive pattern of correlation. Functional analysis of target mRNAs revealed their involvement in inflammatory response, axonal guidance and changes in extracellular matrix. In situ hybridization of miR-132 revealed ubiquitous, neuronal expression not only in the dentate gyrus but also in other brain structures. CONCLUSIONS: QPCR confirmed alterations in miRNAs expression obtained using global profiling method. In chronic epilepsy, changes in expression level of selected miRNA correlate with disease phenotype. Potential mRNAs targets of selected miRNAs may play a role in processes accompanying epilepsy. Expression of miR-132 is cell specific.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2015
• Tom: 75
• Numer: Supl.
• Opis fizyczny: p.S78

Twórcy

autor

Bot A.

• Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland

autor

Debski K.

• Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland

autor

Lukasiuk K.

• Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland