Fig. 6

Inhibition of glutamatergic signaling partially rescues aberrant gene expression of epilepsy candidate genes and associated epigenetic changes. a Calcium imaging 7 days after stimulation with glutamate, glutamate and NBQX/AP5, glutamate and TTX or sham controls. Mean of spike frequency and spike amplitude of recorded neurons during the recorded period of time are shown. b Relative quantification (2^-∆∆Ct) of Gria2 and Grin2a mRNA levels at 2 different time points (3 h and 3 days) after glutamate exposure with TTX or NBQX/AP5 compared to control treatment. c Chromatin immunoprecipitation of histone modification H4ac at the promoter region of Gria2 and Grin2a at 2 different time points (3 h and 3 days) after glutamate treatment with TTX or NBQX/AP5. Data are expressed as mean fold change over control treatment plus standard deviation after normalization to positive control region of the corresponding antibody. d Schematic presentation of the effect of inhibitors TTX, NBQX and AP5 and glutamate signaling as well as common calcium signaling pathways translating external cues into changes in gene expression. AMPA - α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid; AP5 - D-amino-5-phosphonovaleric acid; C – control; CaMK – Calcium/Calmodulin dependent kinase; d – days; Glu – glutamate; h – hours; MAPK – MAP kinase; mGluR – metabotropic glutamate receptor; NBQX - 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo-quinoxaline-2,3-dione; NMDA - N-methyl-D-aspartate; PKA – protein kinase A; TTX – tetrodotoxin; w - weeks