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. 2010 Sep;20(9):1047-60.
doi: 10.1002/hipo.20703.

Aging alters the expression of genes for neuroprotection and synaptic function following acute estradiol treatment

Kristina K Aenlle  1 , Thomas C Foster
Affiliations

Aging alters the expression of genes for neuroprotection and synaptic function following acute estradiol treatment

Kristina K Aenlle et al. Hippocampus. 2010 Sep.

Abstract

This study used microarray analysis to examine age-related changes in gene expression 6 and 12 h following a single estradiol injection in ovariectomized mice. Estradiol-responsive gene expression at the 6 h time point was reduced in aged (18 months) animals compared with young (4 months) and middle-aged (MA, 12 months) mice. Examination of gene clustering within biological and functional pathways indicated that young and MA mice exhibited increased expression of genes for cellular components of the synapse and decreased expression of genes related to oxidative phosphorylation and mitochondrial dysfunction. At the 12 h time point, estradiol-responsive gene expression increased in aged animals and decreased in young and MA mice compared with the 6 h time point. Gene clustering analysis indicated that aged mice exhibited increased expression of genes for signaling pathways that are rapidly influenced by estradiol. The age differences in gene expression for rapid signaling pathways may relate to disparity in basal pathway activity and estradiol mediated activation of rapid signaling cascades.

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Figures

Figure 1
Figure 1
Estradiol-responsive gene expression is altered over the course of aging. A) Illustration of the number of probes that were increased or decreased by estradiol treatment in young (Young), middle-aged (MA) and aged (Aged) animals at 6 hr (filled bars) or 12 hr (open bars) after a single estradiol injection. MA animals exhibited over two times the number of altered probes at 6 hr relative to the other two age groups. The number of altered probes decreased at 12 hr relative to 6 hr for young and MA animals. In contrast, aged animals exhibited approximately a five fold increase in the number of estradiol-responsive probes during this time period. B&C) Venn diagrams of the number of differentially expressed probes in response to estradiol treatment at B) 6 hr and C) 12 hr. The numbers in parentheses represent probes that changes in opposite directions.
Figure 2
Figure 2
Validation of estradiol treatment effects in young animals at 6 hr for six genes using RT-PCR. The bars represent the mean fold change in gene expression for young mice 6 hr following estradiol treatment compared to the mean of age-matched oil treated animals using RT-PCR (open bars) and for microarray measures (filled bars).
See this image and copyright information in PMC

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