Effects of aging on behavioral assessment performance: implications for clinically relevant models of neurological disease

Laboratory investigation

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Object

Despite the role of aging in development of neurological and neurodegenerative diseases, the effects of age are often disregarded in experimental design of preclinical studies. Functional assessment increases the clinical relevance of animal models of neurological disease and adds value beyond traditional histological measures. However, the relationship between age and functional impairment has not been systematically assessed through a battery of functional tests.

Methods

In this study, various sensorimotor and behavioral tests were used to evaluate effects of aging on functional performance in naive animals. Sensorimotor measures included locomotor activity; Rotarod, inclined plane, and grip-strength testing; and modified Neurological Severity Score. The Morris water maze was used to examine differences in learning and memory, and the elevated plus maze and forced swim test were used to assess anxiety-like and depressive-like behaviors, respectively.

Results

Older Sprague-Dawley rats (18–20 months) were found to perform significantly worse on the inclined plane tests, and they exhibited alterations in elevated-plus maze and forced swim test compared with young adult rats (3–4 months). Specifically, older rats exhibited reduced exploration of open arms in elevated plus maze and higher immobility time in forced swim test. Spatial acquisition and reference memory were diminished in older rats compared with those in young adult rats.

Conclusions

This study demonstrates clear differences between naive young adult and older animals, which may have implications in functional assessment for preclinical models of neurological disease.

Abbreviation used in this paper:mNSS = modified Neurological Severity Score.

Article Information

Address correspondence to: Charles L. Rosen, M.D., Ph.D., West Virginia University, One Medical Center Drive, PO Box 9183 Health Sciences Center, Morgantown, West Virginia 26506-9183. email: crosen@hsc.wvu.edu.

Please include this information when citing this paper: published online June 29, 2012; DOI: 10.3171/2012.5.JNS112224.

© AANS, except where prohibited by US copyright law.

Headings

Figures

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    The effect of age on sensorimotor assessment with the grip strength test (A), inclined plane test (B), and total locomotor activity (C). The grip strength and inclined plane tests were significantly different between young adult and older animals (p < 0.05), with older animals exhibiting stronger grip force and young adult animals performing better on the inclined plane. No difference in total locomotor activity was measured. Error bars indicate SEM. Statistical significance was determined using an unpaired t-test. *p < 0.05, **p < 0.01, and ***p < 0.0001.

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    Fixed-speed (left) and accelerating (right) Rotarod test in young adult (light gray bars) and older animals (dark gray bars). The fixed-speed test included trials at 12, 16, 20, 24, 28, 32, 36, and 40 rpm. The accelerating test was conducted over 5 minutes while reaching a maximum speed of 50 rpm. No statistically significant difference was seen between young adult and older animals on either variation of Rotarod testing. Error bars indicate SEM.

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    Reduced performance on the balance beam subtest (part of mNSS) in older animals. Older animals (dark gray bar) were comparable to young adult animals (light gray bar) in all mNSS subtests except for balance beam in which young animals excelled in contrast to older animals. Error bars indicate SEM. Statistical significance was determined using an unpaired t-test. *p < 0.05.

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    Effect of age on behavior using the elevated plus maze assessment. Older animals (dark gray bars) spent less time in the open arms (A) and made fewer entries into the open arms (B), but the groups did not differ in terms of average speed in the open arms (C). In the closed arms, young animals (light gray bars) explored more readily than the older animals, resulting in a higher average speed within the closed arms (D). Error bars indicate SEM. Statistical significance was determined using an unpaired t-test. *p < 0.05 and **p < 0.01.

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    Effect of age on total immobility time, immobile episodes, distance traveled, and speed in the forced swim test. Older animals (dark gray bars) spent more time immobile (A) and had a greater number of immobile episodes (B), but they traveled a similar distance (C) at a similar speed (D). There was no statistically significant difference in latency to first immobile episode (E). Error bars indicate SEM. Statistical significance was determined using an unpaired t-test. *p < 0.05.

  • View in gallery

    The role of age in spatial acquisition determined using the Morris water maze. Older animals (dark gray bars) exhibited increased latency (left) and distance to platform (right) when compared with young animals (light gray bars) at later time points, despite being nearly identical when first exposed to the maze. Error bars indicate SEM. Statistical significance was determined using 2-way ANOVA with Bonferroni post hoc test. *p < 0.05, **p < 0.01, and ***p < 0.001.

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    Reduction in reference memory in older animals as measured in the Morris water maze probe test. Older animals made fewer entries (A), spent less time (B), and traveled a shorter distance (C) in the counter zone than the young animals. The proximity average (D) was lower among young animals, indicating greater reference memory ability. Error bars indicate SEM. Statistical significance was determined using an unpaired t-test. *p < 0.05, **p < 0.01, and ***p < 0.0001.

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