| BackgroundWith the aging of the population, there is increasing emphasis on aging-related research. Although abundant evidence indicates that aging accompanies with behavioral changes especially cognitive decline and many factors (such as psycho-social environment, lifestyles) can affect these behaviors, these studies mainly focus on learning and memory without evaluating other behaviors, moreover their conclusions are not always consistent. Rodents play a vital role in the studies of development of brain aging, and mice model has become a growing concern in age-related behavioral changes. Therefore, it is beneficial to explore the behavioral changes in the aging process and their influencing factors for finding aging interventions.Objective①To investigate the behavioral changes in the middle-aged CD-I mice that is most frequently used in Chinese laboratories;②To further investigate the effects of chronic stress and environmental enrichment on age-related behavioral changes in CD-1mice;③To explore the effects of long-term orally administered the extract of mulberry leaves i.e.,1-deoxynojirimycin (DNJ), on age-related behavioral changes in SAMP8mice.MethodsAccording to the above objective, three experiments were designed.Experiment1:Two age groups of CD-1mice (young group aged5months and middle-aged group at age of12months) were used to assess behavioral changes, including species-typical behaviors (burrowing, nesting and hoarding), sensorimotor behaviors (beam walking and tightrope task), spontaneous exploration and anxiety (open field, elevated plus maze and black-white alley), spatial learning and memory (Morris water maze (MWM) and radial six arm water maze (RAWM)) and novel object recognition.Experiment2:CD-I mice were were randomly divided into four groups as follows: normal old control,1,6and10-month-treatment. Normal old control mice did not undergo any treatment. The treatment groups were divided into stressed, stressed+enriched and enriched subgroups. The stressed mice were randomized to receive daily one way of stresses (restraint, illumination or tail suspension), three days a cycle and a totle of four cycles. The enriched mice had access to objects that stimulated their exploratory behavior and permitted social conditions until finishing the behavioral examination. The objects were rearranged every week and different objects were placed on alternate weeks for novelty. The stressed+enriched mice were exposed to stress followed by enriched environment housing. At age of13months old, all mice were conducted to behavioral evaluation, including species-typical behaviors, sensorimotor behaviors, spontaneous exploration and anxiety, spatial learning and memory (MWM) and recognition memory (novel object recognition(NOR), object recognition location (ORL) and episodic-like memory). In addition, normal6-month old mice were used as young control group.Experiment3:SAMP8mice were randomly divided into three groups:blank control,10mg/kg·d DNJ (low-dose) and20mg/kg·d DNJ (high-dose) groups. DNJ-treated mice at3months old were orally administered DNJ mixed with drinking water for6months until the behavioral tests began, and the blank control mice were received normal drinking water. At age of9months, behavioral changes were assessed as previously described in experiment2. Moreover, another3-month-old mice was set as the young control. ResultsExperiment1:The behavioral changes in middle-aged CD-1miceIn the species-typical tasks, the weights hoarded and burrowed in the middle-aged mice were significantly lower than that in the young mice, which was attributable to the female mice. The middle-aged mice showed better performance than the young mice in the beam walking, and only the middle-aged male mice had better performance than the young male mice in tightrope task. During open-field, the elevated plus maze and black-white alley testing, the middle-aged mice exhibited low locomotor activity and high anxiety, which was attributable to the female mice. In the RAWM, the latency and number of errors of the middle-aged mice were significantly longer or more than those of the young mice in both the learning and memory phases, and the cognitive impairment was mainly found in the females. In the MWM, the middle-aged mice had longer latency than the young mice but no difference in the swimming distance in the place learning test, and they showed shorter percentage of distance and time in the target quadrant than the young mice. Meawhile, the middle-aged mice showed the similar performance to the younger mice in the novel object recognition task.Experiment2:The effects of stress and enriched environment on behavioral changes in the middle-aged CD-1miceDuring the species-typical behaviors and sensorimotor testing, age effect, rather than different treatment effect, was found. In the open-field, the elevated plus maze and black-white alley tasks, the middle-aged mice showed low locomotor activity and high anxiety, and pubertal stress could aggravate the age effects but long-term enriched environment could postphone these age-related behavioral changes. In the recognition testing, there were no significant effects of age and treatment in the NOR and ORL. But, the middle-aged mice exhibited lower preferential index of exploring object than the young mice in the episodic-like memory task, indicating that the middle-aged mice had impaired episodic-like memory. And, stress experienced in different periods (in particular1and6months old) could accelerate episodic-like memory decline and enriched environment could delay this decline. In the MWM, the middle-aged mice had longer latency and swimming distance than the young mice and1-month-stressed mice, but shorter than1-month-enriched mice. The stressed mice showed longer latency and swimming distance than the enriched mice, especially in the1-and6-months stressed mice. The middle-aged mice spent less time and distance in the target quadrant than the young,1-and10-month-stresed+enriched mice, andl,6,10-month enriched mice.1,6, and10-month-stressed mice also spent more time and distance than the same age experienced stresed+enriched and enriched mice.Experiment3:The effects of DNJ on the age-related behavioral changes in SAMP8miceThere was insignificant difference of body weight between DNJ-treated group and control group. In the species-typical behaviors, the older control mice exhibited lower performance than the young mice in the nesting and burrowing, and low dose DNJ treated mice had better performance than the control mice in the nesting. In the tightrope and beam walking, the older control mice had worse performance in these tasks than the young mice, and DNJ treated mice had better performance than the control mice. During spontaneous exploration and anxiety testing, the older control mice showed low exploration activity and anxiety, and DNJ treatment could delay these behavioral changes. In the NOR task, the older control mice had lower preferential index of exploring the novel object than the young mice in the10min delay choice, and DNJ treated mice exhibited higher preferential index than the control mice. In the ORL task, the older control mice showed lower preferential index of exploring object than the young mice in the10min-and24h-delay choices, and DNJ treated mice had higher preferential index than the control mice only in the10min-delay choice. During the episodic-like memory task, the older control mice had lower preferential indexes than the young and DNJ treated mice. In the MWM, the older control mice showed longer swimming distance and latency than the young mice and shorter than DNJ treated mice in the place learning test, and they spent shorter swimming distance and time in the target quadrant than the young and low dose DNJ treated mice.Summary1. Middle-aged CD-1mouse have exhibited some behavioral changes, including low species-typical behaviors, spontaneous exploratory and spatial learning and memory, and high anxiety and sensorimotor. These behavioral changes are attributable to the females, suggesting that CD-1may be an excellent aging model.2. Stress and enrichment experienced in different period do not affect species-typical behaviors, sensorimotor, NOR and ORL in the middle-aged CD-1mice. Chronic stress experienced before middle age can aggravate some behavioral changes in middle-aged mice, including spontaneous exploratory, anxiety, episodic-like memory and spatial learning and memory. But, long-term enrichment can delay these behavioral changes. Moreover, these effects depend on onset time.3. Long-term administrated DNJ do not affect growth development in SAMP8mice, but it can delay age-related behavioral changes, including species-typical behaviors sensorimotor, anxiety, non-spatial and spatial learning and memory. Therefore, DNJ may have the property of anti-brain aging.ConclusionSome behavioral changes have occurred in middle age, but their changeable patterns are different. Moreover, life event and social environment can affect these behavioral changes. The earlier it is, the stronger the effect is. In addition, lifestyles or some food additives can delay aging-related behavioral changes. |
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