Life-long environmental enrichment differentially affects the mnemonic response to estrogen in young, middle-aged, and aged female mice

Abstract

The present study was designed to examine whether life-long exposure to standard or enriched housing affects the ability of estrogen to improve spatial and object memory throughout the lifespan. Three week-old female mice were maintained in standard or enriched housing up to and through ovariectomy and behavioral testing at 5, 17, or 22 months of age. Spatial memory was tested in the Morris water maze and object memory was tested using an object recognition task. Immediately after training each day, mice were injected intraperitoneally with vehicle or 0.2 mg/kg 17β-estradiol. Among young females, object recognition was enhanced by estradiol alone, an effect that was reduced by enrichment. In contrast, spatial water maze performance was impaired by estradiol alone, but improved by the combination of both estradiol and enrichment. At middle-age, object recognition was enhanced by estradiol or enrichment alone, and the combination of both treatments. Spatial memory in the water maze was also improved by both treatments at middle-age, but the beneficial effects of estradiol were limited to standard-housed females. Finally, whereas enrichment in aged females significantly enhanced performance in both tasks, estradiol had no effect at this age in either task. In total, the data indicate that life-long enrichment can significantly alter the extent to which estradiol affects memory in mice throughout the lifespan. Importantly, the interaction between these treatments is highly dependent on age and type of memory tested.

Epigenetic alterations regulate estradiol-induced enhancement of memory consolidation

“…Novel object recognition, conducted as previously reported (29), evaluated nonspatial hippocampal memory (30). Briefly, mice were habituated to an empty white chamber by allowing them to freely explore for 5 min (no data were collected).…”

“…Time spent with each object was recorded; because mice inherently prefer to explore novel objects, a preference for the novel object [more time than chance (15 s) spent with the novel object] indicates intact memory for the familiar object. Vehicletreated mice remember the familiar object after 24 h, but not 48 h (29), and thus a 48-h delay is used to observe memory-enhancing effects of E 2 .…”

The influence of enriched environment on spatial memory in Swiss mice of different ages

“…While some found significant positive effects on spatial memory only in aged mice 7 , other studies also demonstrated such effects in middle-aged mice 6 . Still, some studies have reported improvement on spatial task execution by both young and young adult mice groups 8,9,10,12 . However, studies conducted with mice in age groups similar to those used here did not find significant results for spatial memory tasks 7,8,15 .…”

“…Nevertheless, we did not obtain significant results, which is in accordance with studies that used similar housing periods ( from six to eight weeks) and complex EE protocols (cognitive and physical stimulation and social interaction) 7,8,15 . On the other hand, those studies with significant results in relation to spatial memory, despite using similar enrichment protocols, maintained the EE for longer periods, from 2 to 21 months 9,10,12 . Some of the groups that reported significant results with an EE period and enrichment protocol similar to this study 6,7,8 evaluated middle-aged and aged mice.…”

“…Nevertheless, physical stimulation seems to benefit spatial memory at ages when there is still no memory impairment 22 , likely by promoting changes in glial cells involved in synaptic remodeling and affecting brain plasticity 23 . Studies that used more than one running wheel in their EE protocol reported positive results 8,9,10 . This could be explained by enhanced overall effects due to greater access to physical stimulation, which is associated with higher exposure time to the stimulus.…”