Effects of environmental enrichment on spatial memory and neurochemistry in middle-aged mice

Abstract

The present study compared the effects of environmental enrichment on spatial memory, glutamic acid decarboxylase (GAD) activity, and synaptophysin levels in middle-aged male and female mice. Prior to testing, a subset of 18-month-old male and female C57BL/6 mice was housed with two to three toys and a running wheel in the home cage for up to 29 d. Adult mice (7 mo) of both sexes and the remaining middle-aged mice were group (social) housed, but not exposed to enriching objects. After the enrichment period, all mice were tested in a 1-day version of the Morris water maze, in which both spatial and nonspatial memory were assessed. Immediately after testing, the hippocampus and frontoparietal cortex were dissected, and GAD activity and synaptophysin levels were measured. Environmental enrichment reduced the age-related impairment in spatial acquisition and retention; relative to adult social controls, middle-aged enriched mice were unimpaired, whereas middle-aged social controls were impaired. This reduction was similar in middle-aged males and females. Enrichment did not affect cued memory in either sex. Although hippocampal GAD activity was increased by enrichment in males, all other neurochemical measurements were unaffected by enrichment or aging in either sex. These data suggest that environmental enrichment initiated at middle age can reduce age-related impairments in spatial memory in males and females, although the underlying neurobiological mechanisms of this effect remain unknown.

Figure 1

Environmental enrichment reduced age-related impairments in acquisition of the spatial task in middle-aged enriched males relative to middle-aged social control males. Swim time (A), swim distance (B), and corridor ratio (C) were recorded during each block of four spatial trials. Each point represents the mean ± SEM of each group for four trials. Middle-aged social control males exhibited significantly slower swim times, longer swim distances, and less time in the corridor than adult social control males. In contrast, middle-aged enriched males and adult social control males did not differ in any measure. Open square represents adult social control males; open circle, middle-aged social control males; closed circle, middle-aged enriched males. Group means are shown in Table 2.

Figure 2

Enrichment also reduced the age-related memory impairment of males during the spatial probe trial. This improvement was particularly evident in the proximity measure (B), in which middle-aged social control males swam further from the platform location than adult social control males (*P < 0.05), whereas middle-aged enriched males and adult social control males did not differ. Quadrant time (A), proximity (B), and platform crossings (C) are presented. Open bar represents adult social control males; cross-hatched bar, middle-aged social control males; solid bar, middle-aged enriched males. Each bar represents the mean ± SEM for each group.

Figure 3

Neither age nor enrichment affected cued task performance in either sex. Swim time in males (A) and females (B)are presented. Open circles represent adult social controls, open squares represent middle-aged social controls, and filled circles represent middle-aged enriched. Each point represents the mean ± SEM of each group for one trial.

Figure 4

Environmental enrichment reduced age-related impairments in acquisition of the spatial task in middle-aged enriched females relative to middle-aged social control females. Swim time (A), swim distance (B), and corridor ratio (C) were recorded during each block of four spatial trials. Each point represents the mean ± SEM of each group for four trials. Middle-aged social control females exhibited significantly slower swim times, longer swim distances, and less time in the corridor than adult social control females. In contrast, middle-aged enriched females and adult social control females did not differ in any measure. Furthermore, middle-aged social control females swam longer distances from the platform than middle-aged enriched females. Open squares represent adult social control females; open circles, middle-aged social control females; closed circles, middle-aged enriched females. Group means are shown in Table 2.

Figure 5

Enrichment also reduced the age-related memory impairment of females during the spatial probe trial. Similar to males, this improvement was particularly evident in the proximity measure (B), in which middle-aged social control females swam further from the platform location than adult social control females (*P < 0.05), whereas middle-aged enriched females and adult social control females did not differ. There was also a strong trend for middle-aged enriched females to spend more time in the correct quadrant than middle-aged social control females. Quadrant time (A), proximity (B), and platform crossings (C) are presented. Open bar represents adult social control females; cross-hatched bar, middle-aged social control females; closed bar, middle-aged enriched females. Each bar represents the mean ± SEM for each group.