Systemic lipopolysaccharide administration impairs retrieval of context–object discrimination, but not spatial, memory: Evidence for selective disruption of specific hippocampus-dependent memory functions during acute neuroinflammation

Abstract

Neuroinflammation is implicated in impairments in neuronal function and cognition that arise with aging, trauma, and/or disease. Therefore, understanding the underlying basis of the effect of immune system activation on neural function could lead to therapies for treating cognitive decline. Although neuroinflammation is widely thought to preferentially impair hippocampus-dependent memory, data on the effects of cytokines on cognition are mixed. One possible explanation for these inconsistent results is that cytokines may disrupt specific neural processes underlying some forms of memory but not others. In an earlier study, we tested the effect of systemic administration of bacterial lipopolysaccharide (LPS) on retrieval of hippocampus-dependent context memory and neural circuit function in CA3 and CA1 (Czerniawski and Guzowski, 2014). Paralleling impairment in context discrimination memory, we observed changes in neural circuit function consistent with disrupted pattern separation function. In the current study we tested the hypothesis that acute neuroinflammation selectively disrupts memory retrieval in tasks requiring hippocampal pattern separation processes. Male Sprague-Dawley rats given LPS systemically prior to testing exhibited intact performance in tasks that do not require hippocampal pattern separation processes: novel object recognition and spatial memory in the water maze. By contrast, memory retrieval in a task thought to require hippocampal pattern separation, context-object discrimination, was strongly impaired in LPS-treated rats in the absence of any gross effects on exploratory activity or motivation. These data show that LPS administration does not impair memory retrieval in all hippocampus-dependent tasks, and support the hypothesis that acute neuroinflammation impairs context discrimination memory via disruption of pattern separation processes in hippocampus.

Inducible nitric oxide inhibitor aminoguanidine, ameliorates deleterious effects of lipopolysaccharide on memory and long term potentiation in rat

“…Because of a high density of cytokine receptors [35], hippocampus as an important responsible area for consolidation of spatial memory and LTP induction could be vulnerable to neuro-inflammation [36]. It has been well documented that immune system stimuli such as LPS disturb hippocampusdependent learning processes including learning of spatial tasks and contextual consolidation [37]. LPS also attenuates spatial memory through the reduction of the number and the size of new neurons in dentate gyrus [38].…”

Lipopolysaccharide-induced memory impairment in rats is preventable using 7-nitroindazole

“…Due to a high density cytokines receptors, hippocampus has been considered to be very vulnerable to inflammation 27 . Using animal models, it has been indicated that administration of cytokines or other immune system stimuli including LPS deteriorate hippocampus-dependent learning and memory process 24 . Recently, the brain tissues oxidative damage was considered to have an important role in deleterious effects of LPS on learning and memory 16 .…”

“…All these findings confirm the results of our study. During inflammation responses, microglia as the principle effectors of immune system in the brain, release pro-inflammatory cytokines which directly affects neuronal function including long-term potentiation, glutamate release and cell signaling pathways 24 . LPS has been shown that triggers the overproduction of pro-inflammatory cytokines such as TNF α , IL-1β , IL-6 13,25 .…”

Posttraumatic stress disorder: A metabolic disorder in disguise?

“…More recently, studies have elucidated the mechanism by which inflammation interferes with the acquisition and extinction of fear. Specifically, LPS administration disrupts cellular processes in the hippocampus critical for memory formation (Czerniawski et al, 2015), and increases in IL-6 (Burton and Johnson, 2012) and IL-1β (Gonzalez et al, 2013) interfere in this LPS-induced deficit in memory. Additionally, site-specific injections of both IL-6 (Hao et al, 2014) and TNFα (Jing et al, 2015) into the amygdala impair the acquisition and extinction of fear conditioning.…”