Minor Changes in Gene Expression in the Mouse Preoptic Hypothalamic Region by Inflammation-Induced Prostaglandin E 2

• We investigated to what extent inflammation-induced prostaglandin E 2 (PGE 2 ) regulates gene expression in the central nervous system. Wild-type mice and mice with deletion of the gene encoding microsomal prostaglandin E synthase-1 (mPGES-1), which cannot produce inflammation-induced PGE 2 , were subjected to peripheral injection of bacterial wall lipopolysaccharide (LPS) and killed after 5 h. The median and medial preoptic nuclei, which are rich in prostaglandin E receptors, were isolated by laser capture microdissection (LCM), and subjected to whole genome microarray analysis. Although the immune stimulus induced robust transcriptional changes in the brain, as seen by a quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) on selected genes, only small PGE 2 -dependent gene expression changes were observed in the gene array analysis and, for only two genes, a pronounced differential expression between LPS-treated wild-type and mPGES-1 knockout mice could be verified by qRT-PCR. These were Hspa1a and Hspa1b , encoding heat shock proteins, which showed a two- to three-fold higher expression in wild-type mice than in knockout mice after immune challenge. However, the induced expression of these genes was found to be secondary to increased body temperature because they were induced also by cage exchange stress, which did not elicit PGE 2 synthesis, and thus were not induced per se by PGE 2 -elicited transcriptional events. Our findings suggest that inflammation-induced PGE 2 has little effect on gene expression in the preoptic region, and that centrally elicited disease symptoms, although PGE 2 -dependent, occur as a result of regulation of neuronal excitability that is a consequence of intracellular, transcriptional-independent signalling cascades. Our findings also imply that the profound changes in gene expression in the brain that are elicited by peripheral inflammation occur independently of PGE 2 via a yet unidentified mechanism.

Ämnesord

Medical and Health Sciences  (hsv)

Medicin och hälsovetenskap  (hsv)

MEDICINE  (svep)

MEDICIN  (svep)

Nyckelord

microsomal prostaglandin E synthase-1; prostaglandin E2; fever; preoptic region; laser capture microdissection; whole genome microarray; heat-shock proteins