The role of serum response factor in epileptogenesis

• Autorzy: Nader K. , Kaczmarek L. , Kalita K.
• Języki publikacji: EN

Abstrakty

EN

BACKGROUND AND AIMS: Serum Response Factor is a transcription factor that plays a prominent role in various programs of gene expression in the brain, including neuronal plasticity. Recently, we have shown the inducible-conditional deletion of SRF in the adult mouse hippocampus increased the epileptic phenotype in the kainic acid model of epilepsy, reflected by more severe and frequent seizures. Yet the molecular mechanism underlying these changes remains unknown. In this study we aimed to investigate mechanism of increased epileptogenesis in SRF KO animals using pentylenetetrazol (PTZ) kindling model of epileptogenesis. RESULTS: We showed that SRF knockout animals developed more severe seizures in response to subconvulsive doses of PTZ over time compared to WT littermates. There was no difference in convulsive behavior upon the first PTZ injections in WT and SRF KO animals. To check whether sensitivity to PTZ kindling is related to neuronal sprouting we performed staining for zinc transporter ZnT3 to visualize infrapyramidal mossy fibers. There were no difference in length of mossy fibers between kindled animals from both groups. To further investigate changes in neuronal morphology we analyzed dendritic spines morphology using DiI protocol. Analysis showed no initial differences in dendritic spines density between WT and SRF KO animals in Cornu Ammonis (CA1) and dentate gyrus (DG) field of hippocampus. Next we plan to examine spines morphology in WT and SRF KO animals upon PTZ kindling. To further investigate mechanism of increased SRF KO susceptibility to seizures the level of PSD-95 was analyzed. KO and WT had the same level of PSD-95 under basal condition. In WT mice level of PSD-95 decreased upon PTZ kindling presumably due to homeostatic plasticity mechanisms. However, in SRF KO animals the level of PSD-95 remained at the stable level. CONCLUSION: Taken together these results suggest that SRF transcription factor may play a role in the aberrant plasticity observed in epilepsy.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2015
• Tom: 75
• Numer: Supl.
• Opis fizyczny: p.S79-S80

Twórcy

autor

Nader K.

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

autor

Kaczmarek L.

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

autor

Kalita K.

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