Acute and chronic lipopolysaccharide-induced stress changes expression of proinflammatory cytokine genes in the rat brain region-specifically and affects learning and memory

Abstract

The purpose of the current work was a comparative analysis of the effects of acute and chronic lipopolysaccharide stress on behavior of rats in the Morris water maze and expression of mRNA proinflammatory cytokines and BDNF in different brain structures. The relevance of this study is related with a weak knowledge of the effects of acute and chronic stress on manifestation of cognitive brain functions, ambiguity of influences of both stresses on the hypothalamic-pituatary axis and expression of the proinflammatory cytokines genes, as well as contradictory data in the literature. In experiments on rats, the acute lipopolysaccharide (LPS) stress improved learning in the Morris water maze. For the period of learning, the rats swam on average less distance to reach a hidden platform and spent less time in the outer zone of the pool (tigmotaxis) and had a low speed compared to the control animals and a group of rats with chronic LPS stress. In a probe trial without a platform in the pool there were no significant differences between groups on time spent in the platform quadrant and distance swum. The acute stress produced a substantial increase of TNF-α and IL-1β concentration in the hippocampus and amygdala, but not in the frontal cortex relative to the control animals. Although the chronic stress increased the levels of TNF-α and IL-1β in the amygdala and hippocampus compared to the control groups, the significance between the groups was only marginal and the concentration of BDNF did not differ from the control animals in none of the structures mentioned. The concentration of IL-6 marginally increased in acute LPS stress in the amygdala and marginally decreased chronic LPS stress in the hippocamus relative to the saline control groups. In total, the most clear molecular-biochemical changes occurred in the amygdala and hippocampus, where the increase of interleukines TNF-α and IL-1β were seen in the acute and chronic LPS stress and no changes in BDNF concentration in the frontal cortex.