Effect of chronic intracerebroventricluar administration of lipopolysaccharide on connexin43 protein expressionin rat hippocampus

Hippocampal damages, which are accompanied by inflammation, are among the main causes of epilepsy acquisition. We previously reported that chronic intracerebroventricular [i.c.v.] injection of lipopolysaccharide [LPS] modulates epileptogenesis in rats. There is a network of gap junction channels in the hippocampus that contribute to epileptogenesis. Gap junction channels are formed by oligomeric protein subunits called connexins [Cx]. Astrocytic Cx43 and neuronal Cx36 are expressed in the hippocampus. In order to find out the possible role of gap junctions in seizure-modulating effect of LPS and neuroinflammation, we studied the effect of central administration of LPS on expression of Cx36 and Cx43 in rat hippocampus. LPS, 2.5 micro g/rat/day, was injected i.c.v. to male Wistar rats for 14 days. mRNA and protein abundance of Cx36, Cx43 and IL1-beta were measured in rat hippocampus by real time-PCR, Western blot and ELISA techniques, at the beginning, in the middle, and at the end of the treatment period. IL1-beta protein level was significantly increased 6 h after first injection of LPS. Cx36 and Cx43 mRNA expression did not alter during chronic administration of LPS. A selective decrease in Cx43 protein expression was observed after 7 injections of LPS. It is suggested that Cx43 containing gap junctions in the hippocampus is down-regulated in response to chronic injection of LPS. This event can inhibit propagation of toxic and noxious molecules to neighboring cells and modulate hippocampal excitability and epileptogenesis

Upregulation of connexins 30 and 32 gap junctions in rat hippocampus at transcription level by chronic central injection of lipopolysaccharide

Gap junctions composed of connexins [Cx] are functional in cell defense by propagation of toxic/death molecules to neighboring cells. Hippocampus, one of the brain regions with particular vulnerability to damage, has a wide network of gap junctions. Functional response of astrocytic Cx30 and neuronal Cx32 to hippocampal damage is unknown. We infused lipopolysaccharide [LPS] intracerebroventricularly [2.5 microg/rat] once daily for two weeks to create neuroinflammation. The mRNA and protein levels of the Cx were measured in the hippocampus after 1[st], 7[th] and 14[th] injection by real-time PCR and Western-blot techniques. A significant increase in Cx32 and Cx30 gene expression was observed after 7[th] and 14[th] injection of LPS with no significant change in their protein abundance. Transcriptional overexpression of hippocampal Cx30 and Cx32 could be an adaptive response to production of intracellular toxic molecules but it is not accompanied with post- transcriptional overexpression and might have no functional impact