Profiling psychomotor and cognitive aging in four-way cross mice

Abstract

In part due to their genetic uniformity and stable characteristics, inbred rodents or their F1 progeny are frequently used to study brain aging. However, it is recognized that focus on a single genotype could lead to generalizations about brain aging that might not apply to the species as a whole, or to the human population. As a potential alternative to uniform genotypes, genetically heterogeneous (HET) mice, produced by a four-way cross, were tested in the current study to determine if they exhibit age-related declines in cognitive and psychomotor function similar to other rodent models of brain aging. Young (4 months) and older (23 months) CB6F1 × C3D2F1 mice were administered a variety of tests for cognitive, psychomotor, and sensory/reflexive capacities. Spontaneous locomotion, rearing, and ability to turn in an alley all decreased with age, as did behavioral measures sensitive to muscle strength, balance, and motor coordination. Although no effect of age was found for either startle response amplitude or reaction time to shock stimuli, the old mice reacted with less force to low intensity auditory stimuli. When tested on a spatial swim maze task, the old mice learned less efficiently, exhibited poorer retention after a 66-h delay, and demonstrated greater difficulty learning a new spatial location. In addition, the older mice were less able to learn the platform location when it was identified by a local visual cue. Because there was a significant correlation between spatial and cued discrimination performance in the old mice, it is possible that age-related spatial maze learning deficits could involve visual or motor impairments. Variation among individuals increased with age for most tests of psychomotor function, as well as for spatial swim performance, suggesting that four-way cross mice may be appropriate models of individualized brain aging. However, the analysis of spatial maze learning deficits in older CB6F1 × C3D2F1 mice may have limited applicability in the study of brain aging, because of a confounding with visually cued performance deficits.

Homer-1a immediate early gene expression correlates with better cognitive performance in aging

“…Both tests are well-established behavioral testing paradigms for the assessment of learning and motor coordination in rodents, and mice specifically (Collier and Coleman 1991). Our results are in agreement with the findings for mice of similar age published by us and others previously (Collier and Coleman 1991;Dubey et al 1996;Forster et al 1996;Sumien et al 2004Sumien et al , 2006.…”

“…The cortex and hippocampus are the primary brain regions involved in spatial learning and memory and responsible for swim maze test performance of rodents Forster et al 1996;Sumien et al 2004Sumien et al , 2006Nguyen 2006). Similarly, cortical and cerebellar networks are critical for motor learning and motor coordination (Hatsopoulos and Suminski 2011;Lamont and Weber 2012), as assessed in the present study by the bridge walking test.…”

“…Spatial learning and memory were measured using a swim maze test as described previously (Sumien et al 2006). Mice were allowed to swim in a steel tank (110 cm diameter, 60 cm deep), filled with opaque water, maintained at 24± 1°C.…”

Coenzyme Q10 supplementation reverses age-related impairments in spatial learning and lowers protein oxidation

“…The magnitude of the age-related impairments of psychomotor function observed in mice on the control diet in the current study was similar to that reported previously (Hengemihle et al 1999;Sumien et al 2004Sumien et al , 2006. The mice receiving the low or high dose of CoQ supplementation exhibited age-related deficits in performance, similar to the control group when tested for balance (bridge walking), coordinated running (rotorod), swimming, muscle strength (wire suspension), and spontaneous activity.…”

“…Spatial learning and memory were measured using a Morris water maze test as described previously (de Fiebre et al 2006;Sumien et al 2006). On a given trial, the mouse was allowed to swim in a 120-cm diameter plastic tank filled to 34 cm from the top edge with colored water (nontoxic white paint) and maintained at 24±1°C.…”