Neurobiology of Aging
Volume 30, Issue 6 , Pages 932-945, June 2009

Estrogen effects on cognition and hippocampal transcription in middle-aged mice

Department of Neuroscience, McKnight Brain Institute, University of Florida, P.O. Box 100244, Gainesville, FL 32610-0244, USA

Received 18 July 2007; received in revised form 6 September 2007; accepted 12 September 2007. published online 22 October 2007.

Abstract 

Young and middle-aged female mice were ovariectomized and given cyclic injections of either estradiol or vehicle treatments. During the fifth week after surgery the Morris water maze was used to assess cognitive function. Age and treatment effects emerged over the course of spatial training such that middle-aged vehicle treated mice exhibited deficits in acquiring a spatial search strategy compared to younger vehicle treated mice and middle-age estradiol treated mice. Following behavioral characterization, mice were maintained on their injection schedule until week seven and hippocampi were collected 24h after the last injection. Hippocampal RNA was extracted and genes responsive to age and estrogen were identified using cDNA microarrays. Estradiol treatment in middle-aged mice altered the expression of genes related to transcriptional regulation, biosynthesis, growth, neuroprotection, and elements of cell signaling pathways. Expression profiles for representative genes were confirmed in a separate set of animals using oligonucleotide arrays and RT-PCR. Our results indicate that estrogen treatment in middle-aged animals may promote hippocampal health during the aging process.

Keywords: Estrogen, Estradiol, Hippocampus, Aging, Microarray

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PII: S0197-4580(07)00378-8

doi:10.1016/j.neurobiolaging.2007.09.004

Neurobiology of Aging
Volume 30, Issue 6 , Pages 932-945, June 2009