Abstract
BackgroundLipopolysaccharide (LPS) induces neuroinflammation and memory deficit. Since polyamines improve memory in various cognitive tasks, we hypothesized that spermine administration reverses LPS-induced memory deficits in an object recognition task in mice. The involvement of the polyamine binding site at the N-methyl-D-aspartate (NMDA) receptor and cytokine production in the promnesic effect of spermine were investigated.MethodsAdult male mice were injected with LPS (250 μg/kg, intraperitoneally) and spermine (0.3 to 1 mg/kg, intraperitoneally) or ifenprodil (0.3 to 10 mg/kg, intraperitoneally), or both, and their memory function was evaluated using a novel object recognition task. In addition, cortical and hippocampal cytokines levels were measured by ELISA four hours after LPS injection.ResultsSpermine increased but ifenprodil decreased the recognition index in the novel object recognition task. Spermine, at doses that did not alter memory (0.3 mg/kg, intraperitoneally), reversed the cognitive impairment induced by LPS. Ifenprodil (0.3 mg/kg, intraperitoneally) reversed the protective effect of spermine against LPS-induced memory deficits. However, spermine failed to reverse the LPS-induced increase of cortical and hippocampal cytokine levels.ConclusionsSpermine protects against LPS-induced memory deficits in mice by a mechanism that involves GluN2B receptors.
Highlights
Lipopolysaccharide (LPS) induces neuroinflammation and memory deficit
Spermine increased and ifenprodil decreased the recognition index on novel object recognition task Figure 2A shows the effect of post-training administration of spermine (0.1 to 10 mg/kg) on the recognition index in the object recognition task
Post-hoc analysis revealed that spermine (1 mg/kg) increased the recognition index, indicating that spermine improved memory
Summary
Lipopolysaccharide (LPS) induces neuroinflammation and memory deficit. Since polyamines improve memory in various cognitive tasks, we hypothesized that spermine administration reverses LPS-induced memory deficits in an object recognition task in mice. It has been shown that intraperitoneal injection of lipopolysaccharide (LPS), a cell-wall component of gram-negative bacteria, induces neuroinflammation, hippocampal cell loss, cognitive impairment, learning deficits and even β-amyloid plaque generation in the hippocampus [1,2], constituting a valid experimental model to study the physiological, behavioral, and emotional aspects of sickness behavior [3]. The N-methyl-D-aspartate (NMDA) receptors seem to be susceptible to the neuroinflammatory challenge, since inflammation decreases the expression of GluN1 [21], GluN2A and GluN2B [22] subunits, and NMDA-dependent long-term potentiation [23] in the hippocampus. This finding is in agreement with previous. It sounds possible that other positive allosteric modulators of the NMDA receptor attenuate LPS-induced cognitive deficits
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