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

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 24 hr 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.

Reversal of age-associated cognitive deficits is accompanied by increased plasticity-related gene expression after chronic antidepressant administration in middle-aged mice

“…Visuospatial ability shows a strong association with age, in both humans and in rodent models (Aenlle et al, 2009;Ennaceur et al, 2008;Hoogendam et al, 2014). This study demonstrated an age-related cognitive deficit in visuospatial memory in healthy middle-aged mice.…”

“…Although severe cognitive deficits notably occur in dementia and neurodegenerative diseases, mild cognitive deficits are also prevalent in otherwise healthy older subjects in both humans and in rodent models (Aenlle et al, 2009;Dumas et al, 2013;Ennaceur et al, 2008;Gautam et al, 2011;Gunstad et al, 2006;Salthouse, 2010). Thus, in the following we focus on the physiology of age-related cognitive changes in otherwise healthy middle-aged subjects as such studies may elucidate early changes in mechanisms of age-related cognitive deficits.…”

Influence of Viral Vector–Mediated Delivery of Superoxide Dismutase and Catalase to the Hippocampus on Spatial Learning and Memory During Aging

“…The authors suggest that aged mice adapt to elevated H 2 O 2 . Transcription of genes regulating redox homeostasis increases during middle age (2,4,47). Thus, the increase in GPx1 expression in aged SOD1 mice may represent an adaptive response.…”

Testosterone modifies the effect of APOE genotype on hippocampal volume in middle-aged men

“…To a large extent, research on estrogen loss in women parallels the work that has been done on testosterone in men, establishing connections with APOE, 37 as well as demonstrating effects on hippocampal structure and gene expression. 38,39 In addition to estrogen, women also experience late-life declines in testosterone. 40 The distinct pattern of age-related changes of testosterone and estrogen in men and women may complicate any potential comparison; nevertheless, the possibility of similar interactions in women warrants future investigation.…”