Neuroinflammation induced by lipopolysaccharide leads to memory impairment and alterations in hippocampal leptin signaling.

Peripheral inflammation promotes immune-to-brain communication, mediated by cytokines that affect brain activity. Lipopolysaccharide (LPS) has been widely used to mimic systemic inflammation, and the adipokine leptin, released in this condition, modulates hypothalamic leptin receptors (ObR), contributing to sickness behavior. In this study, we used the intracerebroventricular (ICV) route for LPS administration in an attempt to evaluate an acute and direct of this pathogen-associated molecular pattern on leptin-mediated signaling in the hippocampus, where ObR has been implicated in modulating cognitive response. We used bilateral ICV injection of LPS (25 μg/ventricle) in 60-day-old male Wistar rats and the analysis were performed 48 h after surgery. Neuroinflammation was characterized in the LPS group by an increase in concentration of IL-1β, COX-2 and TLR4 in the hippocampus as well as glial fibrillary acidic protein (GFAP), indicating an astrocyte commitment. Cognitive damage was observed in the animals of the LPS group by an inability to increase the recognition index during the object recognition test. We observed an increase in the concentration of leptin receptors in the hippocampus, which was unaccompanied by changes in the proteins involved in leptin intracellular signaling (p-STAT3 and SOCS3). Moreover, we found a decrease in leptin concentration in the serum of the animals in the LPS group accompanied by an increase in TNF-α levels. Our results showed that neuroinflammation, even in an acute state, can lead to cognitive impairment and may be associated with leptin signaling disturbances in the hippocampus.
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