Enriched environment and masticatory activity rehabilitation recover spatial memory decline in aged mice

Abstract

Background: To measure the impact of masticatory reduction on learning and memory, previous studies have produced experimental masticatory reduction by modified diet or molar removal. Here we induced spatial learning impairment in mice by reducing masticatory activity and then tested the effect of a combination of environmental enrichment and masticatory rehabilitation in recovering spatial learning at adulthood and in later life. For 6 months (6M) or 18 months (18M), we fed three groups of mice from postnatal day 21 respectively with a hard diet (HD) of pellets; pellets followed by a powdered, soft diet (HD/SD, divided into equal periods); or pellets followed by powder, followed by pellets again (HD/SD/HD, divided into equal periods). To mimic sedentary or active lifestyles, half of the animals from each group were raised from weaning in standard cages (impoverished environment; IE) and the other half in enriched cages (enriched environment; EE). To evaluate spatial learning, we used the Morris water maze.

Results: IE6M-HD/SD mice showed lower learning rates compared with control (IE6M-HD) or masticatory rehabilitated (IE6MHD/SD/HD) animals. Similarly, EE-HD/SD mice independent of age showed lower performance than controls (EE-HD) or rehabilitated mice (EE-HD/SD/HD). However, combined rehabilitation and EE in aged mice improved learning rate up to control levels. Learning rates did not correlate with swim speed.

Conclusions: Reduction in masticatory activity imposed on mice previously fed a hard diet (HD/SD) impaired spatial learning in the Morris water maze. In adults, masticatory rehabilitation recovered spatial abilities in both sedentary and active mice, and rehabilitation of masticatory activity combined with EE recovered these losses in aged mice.

Figure 1

Learning rate on water maze test under different diet regimes, ages, and environments. Graphic representation of diet regime, age, and environmental influences on learning rate of the best five performances of each experimental group on the fourth training day. In the top panel (A), indicated in different colours, are the mean values and standard errors of the learning rates with respective significance values, and in the bottom panel (B) are the individual performances (coloured, solid circles) and mean groups (dark dashes between solid circles). (*) indicates significant differences in learning rates between different diet regimes, (#) significant differences in learning rates between environments, and coloured line connectors differences in learning rates between age.

Figure 2

Total and opposite quadrant travelled distances, representative swimming trajectories, and swimming speed. In the top panels, indicated in different colours, are the mean values and standard errors of the total distances (A) and representative swimming trajectories of each group of animals closer to the mean distance group (B). In the bottom panels are the mean values of opposite quadrant distances (C) and swimming speeds (D). All data plots are expressed as a function of age, environment, and diet regimes. As expected, HD/SD groups, independent of age or environment, swam longer distances both in total and in the opposite quadrant than all other groups. (*) indicates significant differences between different diet regimes, (#) significant differences between environments, and coloured line connectors differences between ages, and the edges of the black line link differences between diet.

Figure 3

Experimental timeline. Female albino Swiss mice were housed either in impoverished or enriched environments (middle panel left) from postnatal days 21 until 180 (6 months old; 6M) or 540 (18 months old; 18M), under one of the following diet regimes: HD groups correspond to continuous pellet diets; HD/SD regimes for 6 or 18 months correspond to alternating pellet and powder diet every 3 or 9 months, respectively; HD/SD/HD regimes for 6 or 18 months correspond to sequences of pellet, powder, and pellet food every 2 or 6 months, respectively. All 6M and 18M animals were submitted to the Morris water maze (middle panel, right) between 180 and 195 and between 540 and 555 postnatal days, respectively. Bottom panel: pellet (hard diet) and powder (soft diet) food. Time is represented in days after birth and increases from left to right.