Age differences in locomotor behavior of C57BL/6N Nia mice: A data management approach

doi:10.1016/0091-3057(87)90365-0

Pharmacology Biochemistry and Behavior

Volume 27, Issue 3, July 1987, Pages 545-551

https://doi.org/10.1016/0091-3057(87)90365-0 Get rights and content

Abstract

Separate age groups of C57BL/6NNia mice were tested for within- and between-session habituation of locomotor behavior using a Digiscan System for simultaneous automated gathering of 23 locomotor variables. A computer program, Raw Data Input Program (RDIP) was developed for the reformatting and transfer of raw data samples to a spreadsheet/database management system, and a method for summarization, analysis and presentation of the multivariate data is described. It is concluded that large samples of multivariate locomotor activity data can be effectively managed using a single microcomputer and commercially available software packages.

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More than 80% of most daily spontaneous activities (assessed in an Omnitech activity monitor) occurred during the last hour of light and 12 h of the dark phase in 8 chow-fed male Sprague-Dawley rats. Thirty additional rats were, therefore, monitored over this 13-h period to assess the relationship of activity to the development and maintenance of diet-induced obesity (DIO) on a diet high in energy, fat and sucrose (CM diet). Nine of 20 rats became obese after 3 months on the CM diet, with 71% greater weight gain than 10 chow-fed controls. Eleven of 20 rats were diet resistant (DR), gaining the same amount of weight as chow-fed rats. Neither initial activity levels nor initial body weights on chow (Period I) differed significantly across retrospectively identified groups. After 3 months on CM diet or chow (Period II), as well as after an additional 3 months after CM diet-fed rats returned to chow (Period III), there were significant inverse correlations (r= −.606 to −.370) between body weight at the time of testing and various measures of movement in the horizontal plane. There was no relationship to dietary content nor consistent correlations of body weight or diet group to vertical movements, an indirect measure of ingestive behavior. Patterns of time spent in the vertical position were significantly different for DIO vs. DR rats in Period III, however. Thus, differences in food intake and metabolic efficiency, rather than differences in nocturnal activity, are probably responsible for the greater weight gain in DIO-prone rats placed on CM diet. Decreased activity associated with increasing body weight may contribute to the persistence of DIO but does not appear to be a major factor.
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The development of strategies for treatment of Alzheimer's disease and other age-associated dementias is an important goal of research in the neurosciences. It is suggested that advances in understanding of the etiology of those disorders would provide the most obvious avenues to development of preventative treatments. Research findings from both clinical investigations and studies of animal models are presented which suggest a neuroimmunologic component in age-associated dementia. Clinical studies suggest an association between dementia and brain-reactive autoantibodies in subsets of patients with Alzheimer's disease. Studies of mice suggest that:
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  1) when compared with normal genotypes, mutant mice with accelerated autoimmunity show learning and memory impairments at earlier chronological ages
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  2) the learning and memory deficits of autoimmune and normal mice are qualitatively similar
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  3) the behavioral deficits of normal aged and autoimmune mice are sensitive to similar Pharmacologic interventions. Overall, these findings suggest that intervention strategies targeting the immune system might be useful in the treatment or prevention of aging-associated dementia. Autoimmune mice would be useful as models for the development and testing of such immune-based interventions.
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Separate age groups of autoimmune NZB/BINJ and non-autoimmune C57BL/BNNia mice were compared for habituation of locomotor activity and its retention over four separate testing sessions spaced at 24-hr intervals. A decline in locomotion (distance in cm) or in the time spent in the center zone as a function of sessions was taken to indicate retention for habituation to stimuli within the test apparatus. The time spent in the center zone decreased as a function of sessions in young and mature C57BL/6NNia mice but failed to show reliable between-session decreases in old (24–26-months) C57BL/ 6NNia mice. When compared with the old C57BL/6NNia mice, young NZB/BINJ mice showed similar impairments. Habituation of locomotion was present in all age groups of C57BL/6NNia mice, but absent in NZB/BINJ mice regardless of age. The retention impairments of 2–4 month old NZB/BINJ mice were attenuated when i.p. injections of 0.04–0.16 mg physostigmine/kg were given just following each habituation session. The effectiveness of physostigmine was substantially reduced when injections were delayed by 20 min or longer following each habituation session. The time-dependent reversal of the aged-like retention deficits by the cholinesterase inhibitor, physostigmine, suggests that cholinergic modulation of memory storage processes may be impaired in NZB/BINJ mice.
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It is suggested that the immune system may play a role in the etiology of age-associated cognitive decline and/or Alzheimer's disease. The relationship between brain-reactive antibodies (BRA) and age-associated cognitive dysfunction is reviewed and discussed. A parallel relationship between BRA increases with age and decline of avoidance learning capacity is described in mouse models. Transfer of immunity from old to young mice was found to accelerate both age-related formation of brain-reactive antibodies and age-related decline of avoidance learning capacity. Short-lived mouse genotypes with accelerated autoimmunity were found to show accelerated age-related declines in their ability to acquire an avoidance response when compared with nonautoimmune mice. Overall, these findings suggest that the immune system could be an important target for development of intervention strategies aimed at extending the intellectually competent period of life. Mice in which autoimmunity is accelerated may be useful as models for the development of such interventions.
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Age differences in locomotor behavior of C57BL/6N Nia mice: A data management approach

Abstract

Behav Neural Biol

Neurobiol Aging

Behav Neural Biol

Behav Neural Biol

Neurobiol Aging

Automating the measurement of locomotor activity

Neurobehav Toxicol Teratol