Time course of hippocampal IL-1 beta and memory consolidation impairments in aging rats following peripheral infection

Abstract

We previously reported that aging F344XBN rats are more vulnerable to disruptions of memory consolidation processes following an injection of Escherichia coli than are young rats. Furthermore, this disruption was specific to hippocampal-dependent memory. In the present study we examined the time course of the proinflammatory cytokine IL-1 beta in young and old rats following a peripheral injection of E. coli. Compared to young rats, aging rats treated with E. coli showed an exaggerated and prolonged up-regulation of IL-1 beta protein in the hippocampus, but not in hypothalamus, parietal cortex, prefrontal cortex, serum or spleen. Aging rats showed greater hippocampal IL-1 beta protein levels than their young counterparts 4h after E. coli, and these levels remained significantly elevated for 8 but not 14 days after E. coli. In a second experiment, aging rats exhibited anterograde memory consolidation impairments 4 and 8 days after an E. coli injection, but not after 14 days. A third experiment revealed that following an E. coli injection, bacterial clearance from the spleen and peritoneum was not impaired in aged rats, suggesting that elevations in hippocampal IL-1 beta were not mediated by impaired clearance in the periphery in aging rats. These data suggest that the exaggerated and prolonged elevation of IL-1 beta, specifically in the hippocampus, may be responsible for hippocampal-dependent memory impairments observed in aging rats following a bacterial infection.

Figure 1

IL-1β protein levels of young and old rats following a peripheral vehicle or E. coli injection at 2h, 4h, 24h, 4d, 8d, &14d in a) hippocampus, b) hypothalamus, c) parietal cortex, d) prefrontal cortex, d) serum, and f) spleen. Note that vehicle samples were collected at 3h & 24h and because they did not differ, were pooled to form just one vehicle control group. ^ = significant difference between E. coli-treated and vehicle-treated groups. * = significant difference between age groups. Error bars indicate ± SEM.

Figure 2

An E. coli or vehicle injection was administered four days prior to contextual fear conditioning. E. coli produced a significant memory impairment in old rats but not in young rats in the test of fear of context (a), a hippocampus-dependent task. Old E. coli-treated rats exhibited significantly less freezing than did old vehicle-treated rats, and young E-coli-treated rats. Young rats showed no difference in freezing between vehicle and E. coli treatments. In the test of fear of the tone (b), a hippocampal-independent task, there were no significant differences between any of the groups during the pre-tone testing session, nor during the post-tone testing session. * = p < .05. Error bars indicate ± SEM.

Figure 3

An E. coli or vehicle injection was administered eight days prior to contextual fear conditioning. E. coli produced a significant memory impairment in old rats compared to those who received only a vehicle injection. Again, this impairment was limited to hippocampal-dependent memory as measured in a test for fear of the context (a). However, there were no differences between the groups in the test for fear of the tone (b), a hippocampal-independent task. * = p < .05. Error bars indicate ± SEM.

Figure 4

An E. coli or vehicle injection was administered 14 days prior to contextual fear conditioning. E. coli produced no memory impairment in old rats compared to those who received only a vehicle injection. This was true for both hippocampal-dependent memory as measured in a test for fear of the context (a), and hippocampal-independent memory as measured in a test for fear of the tone (b). Error bars indicate ± SEM.

Figure 5

Colony forming units (CFUs) from cultured spleen homogenates (a) or peritoneal lavage fluid (b) either 24h or 48h following a peripheral E. coli injection in young and old rats. No differences were found between young and old rats in spleen homogenates. However, young rats showed elevated CFUs in the peritoneal lavage fluid at 24h compared to old rats. However, this difference was no longer significant at 48h. * = p < .05. Error bars indicate ± SEM.