Abstract
BackgroundAging is considered to be associated with progressive changes in the brain and its associated sensory, motor, and cognitive functions. A large number of studies comparing young and aged animals have reported differences in various behaviors between age-cohorts, indicating behavioral dysfunctions related to aging. However, relatively little is known about behavioral changes from young adulthood to middle age, and the effect of age on behavior during the early stages of life remains to be understood. In order to investigate age-related changes in the behaviors of mice from young adulthood to middle age, we performed a large-scale analysis of the behavioral data obtained from our behavioral test battery involving 1739 C57BL/6J wild-type mice at 2–12 months of age.ResultsSignificant behavioral differences between age groups (2–3-, 4–5-, 6–7-, and 8–12-month-old groups) were found in all the behavioral tests, including the light/dark transition, open field, elevated plus maze, rotarod, social interaction, prepulse inhibition, Porsolt forced swim, tail suspension, Barnes maze, and fear conditioning tests, except for the hot plate test. Compared with the 2–3-month-old group, the 4–5- and 6–7-month-old groups exhibited decreased locomotor activity to novel environments, motor function, acoustic startle response, social behavior, and depression-related behavior, increased prepulse inhibition, and deficits in spatial and cued fear memory. For most behaviors, the 8–12-month-old group showed similar but more pronounced changes in most of these behaviors compared with the younger age groups. Older groups exhibited increased anxiety-like behavior in the light/dark transition test whereas those groups showed seemingly decreased anxiety-like behavior measured by the elevated plus maze test.ConclusionsThe large-scale analysis of behavioral data from our battery of behavioral tests indicated age-related changes in a wide range of behaviors from young adulthood to middle age in C57BL/6J mice, though these results might have been influenced by possible confounding factors such as the time of day at testing and prior test experience. Our results also indicate that relatively narrow age differences can produce significant behavioral differences during adulthood in mice. These findings provide an insight into our understanding of the neurobiological processes underlying brain function and behavior that are subject to age-related changes in early to middle life. The findings also indicate that age is one of the critical factors to be carefully considered when designing behavioral tests and interpreting behavioral differences that might be induced by experimental manipulations.Electronic supplementary materialThe online version of this article (doi:10.1186/s13041-016-0191-9) contains supplementary material, which is available to authorized users.
Highlights
Aging is considered to be associated with progressive changes in the brain and its associated sensory, motor, and cognitive functions
Our data revealed age-related physiological changes, including gradual increases in body weight and decreases in body temperature, wire hang latency, and rotarod performance, which are generally consistent with previous reports [33,34,35,36,37,38]. These findings suggest that there are age-related changes from young to middle age in the peripheral and central nervous systems associated with declines in thermoregulation, neuromuscular strength, and motor function in C57BL/6J mice, though the gradual decline in motor function may be explained by an increase in body weight with age
Our study showed that activity suppression ratio in the context test increased at 8 months of age, suggesting that contextual fear memory deficit can occur after middle age in C57BL/6 mice
Summary
Aging is considered to be associated with progressive changes in the brain and its associated sensory, motor, and cognitive functions. In the past two decades, advances in gene targeting technology have enabled us to generate targeted gene mutations in mice, which has increased interest in the use of mutant mouse models to elucidate the relationship between the aging brain and behavior (e.g., [14, 15]) Despite these extensive studies comparing young and aged animals and the increasing interest in mutant models, there is still relatively little information regarding age-related changes in behavior from young adulthood to middle age (approximately 2–12 months of age) in the background strains of mice used to create these mutant mice
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