Neural and behavioral responses to low-grade inflammation

Abstract

Neural and behavioral responses after peripheral immune challenge have been observed in numerous studies. The majority of these studies have utilized relatively high doses of lipopolysaccharide (LPS) as the immune stimulant. Little attention has been given to the effects of LPS dose ranges that simulate low grade-inflammation. The current studies were designed to characterize neural and behavioral responses following low-dose LPS stimulation. Results show burrowing and open field activity was significantly impaired following a single i.p. injection of 10, but not 1, µg/kg of LPS. In addition, following repeated 1 µg/kg LPS administration for 10 days, animals showed the progressive development of motor deficits over time. To correlate behavior with CNS activity, cFos activation was determined in the paraventricular nucleus, nucleus of the solitary tract, central amygdaloid nucleus, and ventrolateral medulla. Data revealed there was a dose-dependent activation in all brain areas examined, but only the PVN showed significant activation by low-dose LPS. Additionally, animals that received 1 µg/kg of LPS for 8 days had PVN cFos activation similar to animals that received a single 10 µg/kg LPS injection. These data demonstrate neural and behavior responses can be induced by low-grade inflammation and chronic exposure to sub-threshold levels of LPS can precipitate significantly heightened neural and behavioral responses.

Altered emotionality, hippocampus-dependent performance and expression of NMDA receptor subunit mRNAs in chronically stressed mice

“…A tendency to displace food pellets is often regarded as not a fully specific indicator of hippocampal dysfunction in rodents (Hart et al, 2012;Kaczmarczyk et al, 2013;Tarr et al, 2012) and its neurobiology is debatable. Hence the finding of a correlation between this behavior and hippocampus-dependent learning in the present study might be potentially important in relating the burrowing behavior to the dorsal hippocampus, as originally proposed (Deacon et al, 2002).…”

Repeated exposure of male mice to low doses of lipopolysaccharide: Dose and time dependent development of behavioral sensitization and tolerance in an automated light–dark anxiety test

“…humans [21,23,33,42,54,63]). Acute administration of relatively low doses of LPS (1.0-50.0 g/kg) has been shown to affect burrowing behavior, locomotor activity, social interactions and cognitive processes in mice and rats [18,22,53,60,62]. Low doses of LPS also induce the release of proinflammatory mediators by murine macrophages and have priming effects on subsequent immune challenges in rats [6,20,32,[45][46][47][48]59].…”

82. Kinetic characteristics of euflammation: The induction of controlled inflammation without overt sickness behavior

“…Interestingly, the kinetic responses to consecutive daily administration of subthreshold levels of LPS and E.coli differed dramatically. We found prior exposure to subthreshold levels of LPS sensitized mice to display a greater sickness behavior response upon subsequent LPS challenges (Tarr et al, 2012). However, following repeated E.coli administration, increased host resistance to the induction of sickness behavior by E.coli was evident if mice received prior challenges with subthreshold levels of E.coli (Chen et al, 2013).…”

“…Sickness/motor deficits were determined by using open field apparatus as previously described (Chen et al, 2013;Tarr et al, 2012). The open field apparatus consisted of an opaque 40×40×25 cm Plexiglas® box divided into a grid pattern.…”