Effects of estrogen treatment on expression of brain-derived neurotrophic factor and cAMP response element-binding protein expression and phosphorylation in rat amygdaloid and hippocampal structures - PubMed (original) (raw)

Comparative Study

Effects of estrogen treatment on expression of brain-derived neurotrophic factor and cAMP response element-binding protein expression and phosphorylation in rat amygdaloid and hippocampal structures

Jin Zhou et al. Neuroendocrinology. 2005.

Abstract

Clinical studies indicate an effect of estrogen (E2) 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 E2 on CREB expression and phosphorylation and BDNF expression in the amygdala and hippocampus, areas involved in emotional processing. Ovariectomized rats were given 10 microg 17beta-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 E2 on calcium/calmodulin kinase (CaMK IV) immunolabeling in the hippocampus. E2 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. E2 increased immunolabeling of CREB and pCREB in the medial and basomedial, but not central or basolateral amygdala. E2 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 E2 increases BDNF expression that may underlie some actions of E2 on affective behavior and indicate neuroanatomical heterogeneity in the E2 effect within the amygdala and hippocampus.

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Figures

Fig. 1

A Photomicrographs of BDNF immunolabeling in amygdaloid structures from ovariectomized (OVX) estrogen (E2)- and vehicle-treated rats. The top panel shows light micrographs at low magnification of BDNF immunogold labeling in the central amygdala (CeA) and medial amygdala (MeA) from E2- and vehicle-treated rats. Scale bar, 400 μm. Photomicrographs from the CeA (second panel) and MeA (third panel) from E2- and vehicle-treated rats are shown at higher magnification. Scale bar, 20 μm. B Quantitation of BDNF immunogold labeling (number of immunogold particles per 100 μm2 area) shows that E2 treatment significantly increases levels of BDNF immunolabeling in specific subdivisions of the amygdala and hippocampus. A significant increase in immunogold labeling is seen in the medial (MeA) (p<0.01) and basomedial (BMA) (p<0.01), but not central (CeA) or basolateral (BLA), amygdala of the E2-treated group (N=6) compared to the OVX control animals (N=6). A significant increase in levels of BDNF immunolabeling is seen in the CA1 (p<0.001) and CA3 (p<0.001) regions of the hippocampus, but not in the CA2, dorsal dentate gyrus (DDG), hilus, or ventral dentate gyrus (VDG) of the E2-treated group (N=6) compared to the OVX control (N=6) animals. Values are the mean ± S. E. M. and are represented as the Mean OD/pixels of area. * Significantly different from vehicle-treated rats.

Fig. 1

Fig. 2

A Photomicrographs of BDNF mRNA signal (in situ PCR) in amygdaloid structures from ovariectomized (OVX) estrogen (E2)- and vehicle-treated rats. The top panel shows light micrographs at low magnification of the levels of mRNA for BDNF in the central amygdala (CeA) and medial amygdala (MeA) from E2- and vehicle-treated rats. Scale bar, 400 μm. Photomicrographs from the CeA (second panel) and MeA (third panel) amygdala from E2- and vehicle-treated rats shows the BDNF mRNA signal at higher magnification. Scale bar = 30 μm. B Quantitation of the BDNF mRNA signal shows a significant increase in levels of BDNF mRNA signal in the medial (MeA) (p<0.01) and basomedial (BMA) (p<0.01), but not central (CeA) or basolateral (BLA), amygdala of the E2-treated (N=5) compared to the control (N=5) group. A significant increase in levels of BDNF mRNA is seen in the CA1 (p<0.001) and CA3 (p<0.001) regions of the hippocampus, but not CA2, dorsal dentate gyrus (DDG), hilus, or ventral dentate gyrus (VDG) of E2-treated group compared to OVX controls. Values are the mean ± S. E. M. and are represented as the Mean OD/100pixels of area. * Significantly different from vehicle-treated rats.

Fig. 2

Fig. 3

A Photomicrographs of CaMK IV immunolabeling in the hippocampus of ovariectomized (OVX) estrogen (E2)- and vehicle-treated rats. The top panel shows light micrographs at high magnification of CaMK IV immunogold labeling in the CA1 and CA3 regions of the hippocampus from E2- and vehicle-treated rats. Scale bar, 30 μm. B Quantitation of BDNF immunogold labeling (number of immunogold particles per 100 μm2 area) shows that E2 treatment significantly increases levels of CaMK IV immunolabeling in specific subdivisions of the hippocampus. A significant increase in immunolabeling is seen in the CA1 (p<0.001) and CA3 (p<0.001) regions of the hippocampus, but not CA2, dorsal dentate gyrus (DDG), hilus or ventral dentate gyrus (VDG) of the E2-(N=6) treated group compared to the OVX control animals (N=6). Values are the mean ± S. E. M. and are represented as the Mean OD/pixels of area. * Significantly different from vehicle-treated rats.

Fig. 4

A Photomicrographs of CREB immunolabeling in amygdaloid structures from ovariectomized (OVX) estrogen (E2)- and vehicle-treated rats. The top panel shows light micrographs at low magnification of BDNF immunogold labeling in the central amygdala (CeA) and medial amygdala (MeA) from E2- and vehicle-treated rats. Scale bar, 400 μm. Photomicrographs from the central (second panel) and medial (third panel) amygdala from E2- and vehicle-treated rats are shown at higher magnification. Scale bar, 30 μm. B Quantitation of CREB immunogold labeling (number of immunogold particles per 100 μm2 area) shows that E2 treatment significantly increases levels of CREB immunolableing in specific subdivisions of the amygdala, but not in any of the subdivisions of the hippocampus. A significant increase in the number of gold particles/100 μm2 is seen in the medial (MeA) (p<0.001) and basomedial (BMA) (p<0.001), but not central (CeA) or basolateral (BLA), amygdala of the E2-treated group (N=6) compared to the ovariectomized control (N=6) animals. No differences were seen in the number of gold particles/100 μm2 in the CA1, CA2, or CA3 regions, or dorsal dentate gyrus (DDG), hilus or ventral dentate gyrus (VDG) of the hippocampus between the E2-treated group and OVX control animals. Values are the mean ± S. E. M. and are represented as the Mean OD/pixels of area. * Significantly different from vehicle-treated rats.

Fig. 4

Fig. 5

A Photomicrographs of pCREB immunolabeling in amygdaloid structures from ovariectomized estrogen (E2)- and vehicle-treated rats. The top panel shows light micrographs at low magnification of pCREB immunogold labeling in the central amygdala (CeA) and medial amygdala (MeA) from E2- and vehicle-treated rats. Scale bar, 400 μm. Photomicrographs from the CeA (second panel) and MeA (third panel) amygdala from E2- and vehicle-treated rats at higher magnification. Scale bar, 30 μm. B Photomicrographs of pCREB immunolabeling from the CA1 and CA3 regions of the hippocampus from ovariectomized estrogen (E2)- and vehicle-treated rats at high magnification. Scale bar, 30 μm. C Quantitation of pCREB immunogold labeling (number of immunogold particles per 100 μm2 area) shows that E2 treatment significantly increases levels of pCREB immunolabeling in specific subdivisions of the amygdala and hippocampus. A significant increase in pCREB immunogold labeling is seen in the medial (MeA) (p<0.001) and basomedial (BMA) (p<0.01), but not central (CeA) or basolateral (BLA), amygdala of the E2-treated group compared to the OVX control animals. A significant increase in immunolabeling is seen in the CA1 (p<0.0001) and CA3 (p<0.0001) regions of the hippocampus, but not CA2, dorsal dentate gyrus (DDG), hilus or ventral dentate gyrus (VDG) of the E2-treated group (N=6) compared to the ovariectomized control (N=6) animals. Values are the mean ± S. E. M. and are represented as the Mean OD/100 pixels of area. * Significantly different from vehicle-treated rats.

Fig. 5

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Effects of estrogen treatment on expression of brain-derived neurotrophic factor and cAMP response element-binding protein expression and phosphorylation in rat amygdaloid and hippocampal structures - PubMed (original) (raw)