Figure 1.

Altered brain-derived neurotrophic factor (Bdnf) gene expression and DNA methylation levels in the epileptic hippocampus are associated with memory deficits. (a) Diagram of experimental setup. (b, c) Epileptic animals displayed hippocampus-dependent memory deficits on test day at 24 h posttraining in the contextual fear conditioning (CFC) and the object location (OL) memory paradigms (CFC:t₍₁₇₎ = 3.41, P < 0.01, n = 10–11; OL:t₍₉₎ = 3.37, P < 0.01, n = 5–6, t-test, *significance relative to non-epileptic group). (d) BdnfmRNA levels were significantly increased in the hippocampus of the non-epileptic, epileptic untrained, and epileptic CFC animals following CFC training compared to non-epileptic untrained controls. BdnfmRNA levels were significantly increased in the hippocampus of the epileptic CFC animals compared to all other groups (F_3,18 = 67.58, P < 0.001, n = 5–6, one-way analysis of variance [ANOVA] with post hoc test, *significance relative to non-epileptic group; ^#significance between experimental groups). (e) Bisulfite sequencing analysis of 12 CpG sites within promoter 4 and the noncoding exon IV of the Bdnf gene revealed a significant decrease in DNA methylation levels in the non-epileptic CFC-trained, epileptic untrained, and epileptic CFC-trained animals compared to the non-epileptic untrained controls. The epileptic CFC group had significantly decreased DNA methylation compared to all other groups (F_3,15 = 11.64, P < 0.001, n = 4–5, one-way ANOVA with post hoc test, *significance relative to non-epileptic group; ^#significance between experimental groups). Error bars are SEM.