A Multivariate Assessment of Age-Related Cognitive Impairment in Octodon degus

Abstract

Aging is a progressive functional decline characterized by a gradual deterioration in physiological function and behavior. The most important age-related change in cognitive function is decline in cognitive performance (i.e., the processing or transformation of information to make decisions that includes speed of processing, working memory, and learning). The purpose of this study is to outline the changes in age-related cognitive performance (i.e., short-term recognition memory and long-term learning and memory) in long-lived Octodon degus. The strong similarity between degus and humans in social, metabolic, biochemical, and cognitive aspects makes it a unique animal model for exploring the mechanisms underlying the behavioral and cognitive deficits related to natural aging. In this study, we examined young adult female degus (12- and 24-months-old) and aged female degus (38-, 56-, and 75-months-old) that were exposed to a battery of cognitive-behavioral tests. Multivariate analyses of data from the Social Interaction test or Novel Object/Local Recognition (to measure short-term recognition memory), and the Barnes maze test (to measure long-term learning and memory) revealed a consistent pattern. Young animals formed a separate group of aged degus for both short- and long-term memories. The association between the first component of the principal component analysis (PCA) from short-term memory with the first component of the PCA from long-term memory showed a significant negative correlation. This suggests age-dependent differences in both memories, with the aged degus having higher values of long-term memory ability but poor short-term recognition memory, whereas in the young degus an opposite pattern was found. Approximately 5% of the young and 80% of the aged degus showed an impaired short-term recognition memory; whereas for long-term memory about 32% of the young degus and 57% of the aged degus showed decreased performance on the Barnes maze test. Throughout this study, we outlined age-dependent cognitive performance decline during natural aging in degus. Moreover, we also demonstrated that the use of a multivariate approach let us explore and visualize complex behavioral variables, and identified specific behavioral patterns that allowed us to make powerful conclusions that will facilitate further the study on the biology of aging. In addition, this study could help predict the onset of the aging process based on behavioral performance.

Keywords: Octodon degus; aging; cognitive performance; long-term memory; multivariate analysis; short-term memory.

Figure 1

Principal component analysis graph of (A) short-term memory and (B) long-term memory processes across age groups. Each symbol represents the age of animals (circle: 12-months-old (n = 6 per group); square: 24-months-old (n = 13 per group); triangle: 38-months-old (n = 6 per group); diamond: 56-months-old (n = 5 per group); inverted triangle: 75-months-old (n = 9 per group). For short-term memory analysis, we used Recognition Index information (RI) from the Social Interaction test and the Novel Local Recognition/Novel Object Recognition test. For long-term memory analysis, the principal component analysis (PCA) included information of latency to the first visit of the escape hole and the reference and working memory errors to find the escape hole during the trials of the Barnes maze test. The F and p values of the one-way PERMANOVA test are plotted.

Figure 2

Association between the first axis of PCA from the short-term memory analysis with the first axis from long-term memory using Spearman' rank correlation coefficient. Each data point represents a degus, and symbols represent the age group of animals (black circle: young degus (12- and 24-months-old); gray circle: aged degus (38-, 56-, and 75-months-old).

Figure 3

Evaluation of the cognitive performance of young group (12-, and 24-months-old, n = 19) and aged group (38-, 56-, and 75-months-old, n = 20): short-term memory measured by (A) the Recognition Index (RI) of the Social Interaction test, (B) the RI of the novel local recognition test, and (C) the RI of the novel object recognition test. Long-term memory measured during the test phase of the Barnes maze: (D) latency to the first visit of the escape hole, (E) reference memory errors to find the escape hole (every first visit of a non-escape hole in each trial), and (F) working memory errors (repeated visits to the same non-escape hole in the same trial). The data were analyzed statistically by one-way ANOVA followed by Tukey's post hoc test.