02 November 2005
Clinical studies indicate an effect of estrogen (E<sub>2</sub>) on affect and cognition, which may be mediated by the cAMP response element-binding protein (CREB) pathway and CREB-related gene target brain-derived neurotrophic factor (BDNF). We investigated the effect of E<sub>2</sub> on CREB expression and phosphorylation and BDNF expression in the amygdala and hippocampus, areas involved in emotional processing. Ovariectomized rats were given 10 µg 17β-estradiol or vehicle for 14 days and expression of components of the CREB signaling pathway, i.e., CREB, phosphorylated CREB (pCREB), and BDNF in amygdala and hippocampus were investigated using immunogold labeling. Levels of BDNF mRNA were determined by in situ reverse-transcriptase polymerase chain reaction. We also examined the effect of E<sub>2</sub> on calcium/calmodulin kinase (CaMK IV) immunolabeling in the hippocampus. E<sub>2</sub> increased immunolabeling and mRNA levels of BDNF in the medial and basomedial amygdala and CA1 and CA3 regions of the hippocampus, but not in any other amygdaloid or hippocampal regions examined. E<sub>2</sub> increased immunolabeling of CREB and pCREB in the medial and basomedial, but not central or basolateral amygdala. E<sub>2</sub> also increased CaMK IV and pCREB immunolabeling in the CA1 and CA3 regions, but not CA2 region or dentate gyrus, of the hippocampus. There was no change in immunolabeling of CREB in any hippocampal region. These data identify a signaling pathway through which E<sub>2</sub> increases BDNF expression that may underlie some actions of E<sub>2</sub> on affective behavior and indicate neuroanatomical heterogeneity in the E<sub>2</sub> effect within the amygdala and hippocampus.