Effects of circulating tumor necrosis factor on the neuronal activity and expression of the genes encoding the tumor necrosis factor receptors (p55 and p75) in the rat brain: a view from the blood–brain barrier
Section snippets
Animals and immunogenic stimuli
Adult male Sprague–Dawley rats (Charles River Canada, St Constant, Québec, Canada; ∼240–275 g) were acclimated to standard laboratory conditions (14-h light/10-h dark cycle; lights on at 06.00 and off at 20.00), with free access to rat chow and water. All efforts were made to minimize animal suffering and to reduce the number of rats used, and all protocols were approved by the Laval University Animal Welfare Committee. A total of 87 rats was assigned to different protocols divided among the
Basal expression of p55 and p75 receptor messenger RNAs
Figure 1 shows representative examples of the rostrocaudal distribution of the gene encoding the TNF-α p55 receptor in the rat brain. Low hybridization signal was detected in non-parenchymal barrier-related structures, such as the ependymal lining cells of the intracerebroventricular wall, the leptomeninges, the choroid plexus and along the blood vessels. The ME/arcuate nucleus, the PVN, the supraoptic nucleus (SON), the AP and the pyramidal layer of the cerebellar cortex exhibited positive p55
Discussion
The present study provides the fine distribution of the genes encoding p55 and p75 in the rat brain under basal conditions and following systemic injections with the bacterial endotoxin LPS and the exogenous ligand for these TNF receptors. Both p55 and p75 mRNAs were visible in unchallenged brains, but the TNF p55 receptor was clearly the most abundant; convincing hybridization signal was detected in the choroid plexus, leptomeninges, ependymal lining cells of the ventricular walls, PVN, SON,
Conclusions
Bebo and Linthicum3 have recently reported that interferon-γ and IL-1β up-regulated the levels of both p55 and p75 TNF receptor mRNAs in mouse cerebrovascular endothelium, while TNF-α had no effect. This latter study was, however, performed using cerebrovascular endothelial cells cultured from experimental autoimmune encephalomyelitis-susceptible (SJL/J) and experimental autoimmune encephalomyelitis-resistant (Balb/c) mice. Our in vivo experiments in conscious and freely moving male rats show a
Acknowledgements
This research was supported by the Medical Research Council of Canada (MRCC). Sylvain Nadeau holds a Studentship from the MRCC and Serge Rivest is an MRCC Scientist. We thank Dr I. Verma (The Salk Institute, La Jolla, CA, U.S.A.) for the generous gift of the rat c-fos cDNA, Dr A. Israel (Institut Pasteur, Paris, France) for the mouse IκB-α cDNA, Dr S. Watson (The University of Michigan, Ann Arbor, MI, U.S.A.) for the pGEM3 plasmid containing a pure CRF intronic piece, Dr Adolf Himmler (Bender &
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