Significance of IL-6 Deficiency in Recognition Memory in Young Adult and Aged Mice

Abstract

Chronic peripheral elevation of interleukin 6 (IL-6) in humans is associated with cognitive deficits. 4- and 24-month-old IL-6-deficient C57BL/6J (IL-6KO) and reference wild-type (WT) mice were tested in an object recognition test. Discrimination ratios and recognition indexes were significantly lower in 4-month-old IL-6KO and in 24-month-old WT mice vs 4-month-old WT animals. Their discrimination ratios had negative values and recognition indexes were below 50% indicating inability to differentiate the novel from the familiar object after 1-hour delay. In 24-month-old IL-6KO mice recognition index reached 53.17% indicating that their recognition memory was not worsened with age in comparison with younger IL-6-deficient animals. Results of holeboard and elevated plus maze indicated that this effect was memory specific. Inborn IL-6 deficiency attenuated recognition memory in 4-month-old mice and did not altered recognition memory in aged animals. IL-6 signalling may constitute a target for development of the protection against memory disturbances connected with IL-6 overexpression.

Keywords: Elevated plus maze; Holeboard; IL-6 deficiency; Mice; Object recognition memory.

Fig. 1

Effect of IL-6 deficiency on locomotor activity measured by a total, b peripheral and c central ambulation, and on exploratory activity measured by d rearings and e head-dips in a holeboard test performed on 4- and 24-month-old IL-6KO and age-matched WT mice. f Central area leaving time was used for the evaluation of anxiety level. Columns represent mean ± SEM of the values obtained from 9–10 animals. Rearings were less frequent in 24-month-old IL-6KO mice (***p < 0.005) and in 4-month-old WT ones (*p < 0.05) in comparison with 24-month-old WT animals (ANOVA and post hoc Bonferroni test)

Fig. 2

Effect of IL-6 deficiency on anxiety level evaluated in an elevated plus maze performed on 4- and 24-month-old IL-6KO and age-matched WT mice. Columns represent mean ± SEM of the values obtained from 9–10 animals. Percent of time spent a in closed arms, and c in central area of the apparatus, f central area latency time and number of entries d to closed arms were comparable in all tested groups. b 4-month-old IL-6KO mice spent significantly longer time (*p < 0.05) and e more frequently visited open arms (**p < 0.01) than 4-month-old WT animals (Kruskal–Wallis test followed by post hoc Dunn’s test)

Fig. 3

Effect of IL-6 deficiency on object’s exploration during T1 and T2 trials in an object recognition test performed on 4- and 24-month-old IL-6KO and age-matched WT mice. Columns represent mean ± SEM of the values obtained from 9–10 animals. A—exploration time of an object presented during T1 trial, A′—exploration time of a duplicate of familiar object presented during T2 trial, B—exploration time of a novel object presented during T2 trial, (B + A′)—the sum of exploration time of both objects presented in T2 trial. 24-month-old IL-6KO mice displayed shorter exploration of object B (ANOVA and post hoc Bonferroni test) and of object A′, as well as of both objects (B + A′) evaluated by Kruskal–Wallis test with Dunn’s post hoc test (*p < 0.05)

Fig. 4

Effect of IL-6 deficiency on a index of discrimination (B − A′), b discrimination ratio (B − A′)/(B + A′) and c recognition index (B x 100)/(B + A′) evaluated in an object recognition test performed on 4- and 24-month-old IL-6KO mice and age-matched WT ones. Columns represent mean ± SEM of the values obtained from 9-10 animals. Discrimination ratios and recognition indexes were significantly lower in 4-month-old IL-6KO and in 24-month-old WT mice in comparison with 4-month-old WT animals (*p < 0.05, Kruskal–Wallis test with Dunn’s post hoc test)