Evidence for age-related decline in spatial memory in a novel allocentric memory task.

Several studies report spatial memory decline in old age. However, few studies have examined whether old adults are specifically impaired in allocentric memory tasks (testing for object-to-object spatial location memory). Thus, the present study examined the effects of age on allocentric spatial memory using a novel landmark memory task. Young (18-25 years old) and old (65 years and older) participants watched 10 short videos that displayed 180-degree viewpoints of distinct real-world locations with landmark cues. After watching each video, participants saw a snapshot from the video and were asked whether a landmark cue previously viewed in the video was to the left or right of the snapshot view. Young adults outperformed old adults on the task. This age-related decline in spatial performance was similar for men and women. These findings support that spatial ability in an allocentric task is sensitive to age-related cognitive decline in men and women.

The Effects of Hormone Contraceptives and Menstruation on Object Memory and Spatial Ability in Young Women.

The aim of this study is to examine the relationship between hormone contraceptive use and menstruation on cognitive performance in young women. The object array task assessed object memory and a mental rotations test assessed spatial ability in women taking hormone contraceptives and naturally cycling women. Women taking hormone contraceptives were significantly better than naturally cycling women at identifying novel objects on an object array, but not on performance of a mental rotations task. There were also no significant differences in either task between naturally cycling women who were menstruating and those who were not menstruating during testing. The results of this study suggest that women taking hormone contraceptives outperformed naturally cycling women in recalling the identities of objects. The findings from this study help to further demonstrate the relationship between ovarian hormones and cognitive performance and add to the understanding of how hormone contraceptives affect cognition.

A new approach to understanding the molecular mechanisms through which estrogens affect cognition.

Traditional approaches to the study of hormones and cognition have been primarily observational or correlational in nature. Because this work does not permit causal relationships to be identified, very little is known about the specific molecules and cellular events through which hormones affect cognitive function. In this review, we propose a new approach to study hormones and memory, where the systematic blocking of cellular events can reveal which such events are necessary for hormones to influence memory consolidation. The discussion will focus on the modulation of the hippocampus and hippocampal memory by estrogens, given the extensive literature on this subject, and will illustrate how the application of this approach is beginning to reveal important new information about the molecular mechanisms through which estrogens modulate memory consolidation. The clinical relevance of this work will also be discussed.

Estradiol-induced enhancement of object memory consolidation involves hippocampal extracellular signal-regulated kinase activation and membrane-bound estrogen receptors.

The extracellular signal-regulated kinase (ERK) pathway is critical for various forms of learning and memory, and is activated by the potent estrogen 17beta-estradiol (E(2)). Here, we asked whether E(2) modulates memory via ERK activation and putative membrane-bound estrogen receptors (ERs). Using ovariectomized mice, we first demonstrate that intraperitoneal injection of 0.2 mg/kg E(2) significantly increases dorsal hippocampal levels of phosphorylated ERK protein 1 h after injection. Second, we show that E(2) administered intraperitoneally (0.2 mg/kg) or via intrahippocampal infusion (5.0 microg/side) immediately after training in an object recognition task significantly enhances memory retention, and that the beneficial effect of intraperitoneal E(2) is blocked by dorsal hippocampal inhibition of ERK activation. Third, using bovine serum albumin-conjugated 17beta-estradiol (BSA-E(2)), we demonstrate that E(2) binding at membrane-bound ERs can increase dorsal hippocampal ERK activation and enhance object memory consolidation in an ERK-dependent manner. Fourth, we show that this effect is independent of nuclear ERs, but is dependent on the dorsal hippocampus. By demonstrating that E(2) enhances memory consolidation via dorsal hippocampal ERK activation, this study is the first to identify a specific molecular pathway by which E(2) modulates memory and to demonstrate a novel role for membrane-bound ERs in mediating E(2)-induced improvements in hippocampal memory consolidation.

Post-training progesterone dose-dependently enhances object, but not spatial, memory consolidation.

The aim of this study was to determine if progesterone modulates object and spatial memory consolidation in young ovariectomized C57BL/6 mice. Object memory was tested in an object recognition task using 24- and 48-h delays. Spatial memory was tested in a 2-day version of the Morris water maze in which retention was tested 24 or 48 h after training. Immediately after training in each task, mice received a single intraperitoneal injection of vehicle or 5, 10, or 20mg/kg water-soluble progesterone. Mice were then tested 24 or 48 h later in the absence of circulating progesterone. Post-training injections of 10 and 20mg/kg progesterone enhanced object recognition, but not memory in the spatial water maze. These findings suggest that object memory consolidation in young female mice is more sensitive to the modulatory effects of progesterone than spatial memory consolidation, at least using the tasks, doses, and delays tested. As such, these findings may have important implications for the design of progesterone therapies intended to reduce age-related memory decline.

Age-dependent effects of environmental enrichment on spatial reference memory in male mice.

Although environmental enrichment has been shown to improve various types of memory in young and aging mice, no study has directly compared the degree to which enrichment improves memory at different ages throughout the lifespan in male mice. Therefore, the present study investigated the effects of long-term continuous enrichment in young (3 months), middle-aged (15 months), and aged (21 months) male C57BL/6 mice. Spatial reference memory was tested in the Morris water maze. Results demonstrate that 24h/day environmental enrichment for approximately 6 weeks significantly improved spatial memory in the Morris water maze in aged males, but not in young or middle-aged males. These data also indicate that 24h exposure to complex enriched housing conditions increases the magnitude of enrichment-induced improvements in memory among aged mice relative to those previously reported by this lab and others.

Single enrichment variables differentially reduce age-related memory decline in female mice.

The authors sought to determine how different elements of enrichment, for example, cognitive stimulation and voluntary exercise, differ in their ability to improve memory throughout the lifespan. Young, middle-aged, and aged female C57BL/6 mice received 24-hr exposure in their home cages to toys alone (cognitive stimulation), running wheels alone (exercise), or both toys and running wheels (complex enrichment) for 4 weeks prior to and then throughout spatial water maze testing. As expected, spatial memory became progressively worse with age. Exercise alone improved spatial water maze performance in young mice, whereas both exercise alone and complex enrichment improved spatial maze performance in middle-aged mice. All enrichment treatments improved spatial maze performance in aged mice. These data suggest that exercise is the most effective element of enrichment in young female mice and that both cognitive stimulation and exercise are necessary to reliably improve spatial water maze performance in aging female mice.

Effects of estrogen and progesterone on spatial memory consolidation in aged females.

Interpretation of data illustrating that estrogen, with or without progestin, is detrimental to memory in post-menopausal women is complicated by the fact that little is known about the effects of progestins on memory. The present study examined if estrogen, alone or with progesterone, affects spatial memory consolidation in ovariectomized aged female mice. Mice received eight training trials in a spatial Morris water maze followed immediately by injection of water-soluble 17beta-estradiol (E(2); 0.2 mg/kg) or vehicle. Mice were re-tested 24 h later. All mice learned to find the platform on Day 1. On Day 2, the performance of control, but not E(2) mice, deteriorated, suggesting that E(2) enhanced memory for the platform location. In a second experiment, mice were injected with E(2) and 10 or 20 mg/kg water-soluble progesterone. The 10 mg/kg dose of progesterone did not affect estrogen's ability to enhance spatial memory consolidation, but 20 mg/kg blocked this effect. These data indicate that estrogen can improve spatial memory consolidation in aged females and that this effect can be attenuated by progesterone.