Increased Bdnf mRNA and protein expression in epilepsy correlates to decreased DNA methylation levels in the epileptic hippocampus. A) Diagram of the CpG sites analyzed in the Bdnf coding exon IX. The putative transcription factor binding sites encompassing CpG sites 2 and 4 are shown that are important for activity-dependent gene transcription. B1) Overall Bdnf DNA methylation levels were decreased in hippocampal areas CA1, CA3 and the DG region from epileptic animals. (CA1, t(5) = 3.22, p = 0.02, n = 6; CA3, t(5) = 7.18, p = 0.0008, n = 6; DG, t(5) = 4.79, p = 0.005, n = 6; student paired t-test, *p<0.05, **p<0.01, ***p<0.001). B2) BDNF DNA methylation analysis across 12 CpG sites at the Bdnf gene in area CA1 demonstrates site-specific CpG methylation changes during the epilepsy phase (Student paired t-test, *p<0.05, n=6). C) Bdnf mRNA levels were significantly increased in hippocampal areas CA1, CA3, and DG region from epileptic animals relative to controls (CA1, t(9) = 2.55, p = 0.03, n = 5-6; CA3, t(11) = 2.37, p = 0.04, n = 6-7; DG, t(14) = 2.50, p = 0.03, n = 6) D) BDNF protein was significantly increased in area CA1 of the epileptic animals relative to controls (t(6) = 2.68, p = 0.04, n = 4). Student unpaired t-test, *p<0.05. Error bars are SEM.