SRF regulates the expression of genes that may control epilepsy

• Autorzy: Kalita K. , Kuzniewska B. , Nader K. , Dabrowski M. , Kaczmarek L.
• Języki publikacji: EN

Abstrakty

EN

BACKGROUND AND AIMS: Although the transcription factor serum response factor (SRF) has been suggested to play a role in activity-dependent gene expression and mediate plasticity-associated structural changes in the hippocampus, no solid evidence has been provided for its role in brain pathology. A genome-wide program of activity-induced genes that are regulated by SRF also remains unknown. RESULTS: In the present study, we showed that the inducible-conditional deletion of SRF in the adult mouse hippocampus increased the epileptic phenotype in the kainic acid model of epilepsy, reflected by increase in the susceptibility to spontaneous seizure development and more severe seizures. Moreover, we observed a robust decrease in activity-induced gene transcription in SRF knockout mice at 6 hours after kainic acid injections. We characterized the genetic program controlled by SRF in neurons and found that SRF target genes are associated with synaptic plasticity and epilepsy. Several of these SRF targets function as regulators of inhibitory/excitatory balance and the structural plasticity of neurons. We also identified novel direct SRF targets in neurons: Npas4, Gadd45g, and Zfp36. CONCLUSIONS: Altogether, our data indicate that proteins that are highly upregulated by neuronal stimulation, identified in the present study as SRF targets, function as endogenous protectors against overactivation by increasing the level of inhibition or modulating dendritic spine number and morphology. Thus, the lack of these effector proteins in SRF knockout animals may lead to uncontrolled excitation and eventually epilepsy.

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

Twórcy

autor

Kalita K.

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

autor

Kuzniewska B.

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

autor

Nader K.

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

autor

Dabrowski M.

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

autor

Kaczmarek L.

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