The Sedentary Lifestyle and Masticatory Dysfunction: Time to Review the Contribution to Age-Associated Cognitive Decline and Astrocyte Morphotypes in the Dentate Gyrus.

As aging and cognitive decline progresses, the impact of a sedentary lifestyle on the appearance of environment-dependent cellular morphologies in the brain becomes more apparent. Sedentary living is also associated with poor oral health, which is known to correlate with the rate of cognitive decline. Here, we will review the evidence for the interplay between mastication and environmental enrichment and assess the impact of each on the structure of the brain. In previous studies, we explored the relationship between behavior and the morphological features of dentate gyrus glial fibrillary acidic protein (GFAP)-positive astrocytes during aging in contrasting environments and in the context of induced masticatory dysfunction. Hierarchical cluster and discriminant analysis of GFAP-positive astrocytes from the dentate gyrus molecular layer revealed that the proportion of AST1 (astrocyte arbors with greater complexity phenotype) and AST2 (lower complexity) are differentially affected by environment, aging and masticatory dysfunction, but the relationship is not straightforward. Here we re-evaluated our previous reconstructions by comparing dorsal and ventral astrocyte morphologies in the dentate gyrus, and we found that morphological complexity was the variable that contributed most to cluster formation across the experimental groups. In general, reducing masticatory activity increases astrocyte morphological complexity, and the effect is most marked in the ventral dentate gyrus, whereas the effect of environment was more marked in the dorsal dentate gyrus. All morphotypes retained their basic structural organization in intact tissue, suggesting that they are subtypes with a non-proliferative astrocyte profile. In summary, the increased complexity of astrocytes in situations where neuronal loss and behavioral deficits are present is counterintuitive, but highlights the need to better understand the role of the astrocyte in these conditions.

Sedentary Life and Reduced Mastication Impair Spatial Learning and Memory and Differentially Affect Dentate Gyrus Astrocyte Subtypes in the Aged Mice.

To explore the impact of reduced mastication and a sedentary lifestyle on spatial learning and memory in the aged mice, as well as on the morphology of astrocytes in the molecular layer of dentate gyrus (MolDG), different masticatory regimens were imposed. Control mice received a pellet-type hard diet, while the reduced masticatory activity group received a pellet diet followed by a powdered diet, and the masticatory rehabilitation group received a pellet diet, followed by powder diet and then a pellet again. To mimic sedentary or active lifestyles, mice were housed in an impoverished environment of standard cages or in an enriched environment. The Morris Water Maze (MWM) test showed that masticatory-deprived group, regardless of environment, was not able to learn and remember the hidden platform location, but masticatory rehabilitation combined with enriched environment recovered such disabilities. Microscopic three-dimensional reconstructions of 1,800 glial fibrillary acidic protein (GFAP)-immunolabeled astrocytes from the external third of the MolDG were generated using a stereological systematic and random sampling approach. Hierarchical cluster analysis allowed the characterization into two main groups of astrocytes with greater and lower morphological complexities, respectively, AST1 and AST2. When compared to compared to the hard diet group subjected to impoverished environment, deprived animals maintained in the same environment for 6 months showed remarkable shrinkage of astrocyte branches. However, the long-term environmental enrichment (18-month-old) applied to the deprived group reversed the shrinkage effect, with significant increase in the morphological complexity of AST1 and AST2, when in an impoverished or enriched environment. During housing under enriched environment, complexity of branches of AST1 and AST2 was reduced by the powder diet (pellet followed by powder regimes) in young but not in old mice, where it was reversed by pellet diet (pellet followed by powder and pellet regime again). The same was not true for mice housed under impoverished environment. Interestingly, we were unable to find any correlation between MWM data and astrocyte morphological changes. Our findings indicate that both young and aged mice subjected to environmental enrichment, and under normal or rehabilitated masticatory activity, preserve spatial learning and memory. Nonetheless, data suggest that an impoverished environment and reduced mastication synergize to aggravate age-related cognitive decline; however, the association with morphological diversity of AST1 and AST2 at the MolDG requires further investigation.

Environmental Impoverishment, Aging, and Reduction in Mastication Affect Mouse Innate Repertoire to Explore Novel Environments and to Assess Risk.

Studies indicate that inhibition of adequate masticatory function, due to soft diet, occlusal disharmony, or molar losses affects the cognitive behavior of rodents. However, no study has tested the effects on new environments exploration and risk assessment coupled with a combination of masticatory function rehabilitation and environmental enrichment. In the present report, we tested the hypothesis that age, environment, and masticatory changes may interact and alter exploratory patterns of locomotor activity and mice preferences in an open field (OF) arena. As OF arenas are widely used to measure anxiety-like behavior in rats and mice. We examined in an open arena, the exploratory and locomotor activities of mature (6-month-old; 6M), late mature (12-month-old; 12M), and aged (18-month-old; 18M) mice, subjected to distinct masticatory regimens and environments. Three different regimens of masticatory activity were used: continuous normal mastication with hard pellets (HD); normal mastication followed by reduced mastication with equal periods of pellets followed by soft powder - HD/SD; or rehabilitated masticatory activity with equal periods of HD, followed by powder, followed by pellets - HD/SD/HD). Under each diet regimen, half of the individuals were raised in standard cages [impoverished environment (IE)] and the other half in enriched cages [enriched environment (EE)]. Animals behavior on the open field (OF) task were recorded by webcam and analyzed with Any Maze software (Stöelting). The locomotor and exploratory activities in OF task declined with age, and this was particularly evident in 18M HD EE mice. Although all groups kept their preference by the peripheral zone, the outcomes were significantly influenced by interactions between environment, age, and diet. Independent of diet regime, 6M young mice maintained in an EE where voluntary exercise apparatus is available, revealed significant less body weight than all other groups. Although body weight differences were minimized as age progressed, 18M EE group revealed intragroup significant influence of diet regimens. We suggest that long life environmental enrichment reduces the tendency to avoid open/lit spaces (OF) and this is particularly influenced by masticatory activity. These measurements may be useful in discussions of anxiety-related tasks.