NR1H4 and Anxiety: Studies have evinced that CREB and BDNF expression levels are down-regulated in the hippocampus of rats with anxiety-like behavior (59, 60), suggesting that the overactivation of FXR in hippocampal neurons by excessive CDCA may target and inhibit the CREB/BDNF pathway via a CREB-dependent mechanism to impair neural function and promote anxiety.