How does peripheral lipopolysaccharide induce gene expression in the brain of rats?
Section snippets
Animal protocol
Groups of male Wistar rats (weighing around 225–270 g) were housed with light–dark cycle such that their adrenocortical activity was highest between 9 and 11 a.m. Prior to the start of the experiment, each rat was familiarized for 1 week with the experimental procedures to reduce stress-induced changes in the HPA axis. Then, the animals were injected with LPS (100 μg/kg) or the vehicle alone (for control) by i.p. injection (Bahrami et al., 1994). At specific time intervals after the injection,
CRF, iNOS, IL-1β and GR mRNA expression, and NO levels in the hypothalamus
Fig. 1 shows the RT-PCR analysis of iNOS, CRF, GR, IL-1β and β-actin mRNA. The IL-1β mRNA was detectable at 0.5 h after and peaked at 4 h after LPS injection. The iNOS mRNA appeared at 0.5 h after and peaked at 2 h after LPS injection. CRF mRNA appeared at 2 h after and peaked at 4 h after LPS injection. GR mRNA appeared at 3 h after and peaked at 6 h after LPS injection. iNOS mRNA values returned to the basal level within 3 to 4 h after LPS exposure. CRF mRNAs returned to the basal level within 6 h
Discussion
Peripheral LPS has been shown to activate a cascade of pro-inflammatory genes including IL-1β and iNOS genes that induce inflammatory reaction in the brain (Chao et al., 1992, Van Dam et al., 1998, Raber et al., 1995, Karanth et al., 1993, Lee et al., 1999, Uribe et al., 1999), although possible mechanism(s) for the central effects of peripheral LPS is not fully understood. In this study, we have hypothesized that either LPS crossed the BBB and directly induced pro-inflammatory cytokine and
Acknowledgements
This project was partially funded by grants from the Graduate School, College of Veterinary Medicine, and Center for Food Safety of the University of Minnesota.
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