Post-traumatic anxiety associates with failure of the innate immune receptor TLR9 to evade the pro-inflammatory NFκB pathway

Post-traumatic anxiety notably involves inflammation, but its causes and functional significance are yet unclear. Here, we report that failure of the innate immune system Toll-like receptor 9 (TLR9) to limit inflammation is causally involved with anxiety-associated inflammation and that peripheral administration of specific oligonucleotide activators of TLR9 may prevent post-traumatic consequences in stressed mice. Suggesting involvement of NFκB-mediated enhancement of inflammatory reactions in the post-traumatic phenotype, we found association of serum interleukin-1β increases with symptoms severity and volumetric brain changes in post-traumatic stress disorder patients. In predator scent-stressed mice, the moderate NFκB-activating oligonucleotides mEN101 and its human ortholog BL-7040, but not the canonic NFκB activator oligonucleotide ODN1826, induced anxiolytic effects. In stressed mice, peripherally administered mEN101 prevented delayed stress-inducible serum interleukin-1β increases while limiting stress-characteristic hippocampal transcript modifications and the anxiety-induced EGR1-mediated neuronal activation. Attesting to the TLR9 specificity of this response, BL-7040 suppressed NFκB-mediated luciferase in transfected cells co-expressing TLR9, but not other TLRs. Furthermore, TLR9−/− mice were mEN101 and BL-7040 resistant and presented unprovoked anxiety-like behavior and anxiety-characteristic hippocampal transcripts. Our findings demonstrate functional relevance of TLR9 in protecting stressed mammals from overreacting to traumatic experiences and suggest using oligonucleotide-mediated peripheral TLR9 activation to potentiate the innate immune system and prevent post-traumatic inflammation and anxiety

The importance of co - authorship and disciplined research

This study reviewed articles in a Pacific Islands Educational Journal from 1978 to 2005 in order to analyse the types of authorship and types of papers published. It was specifically interested in looking at the prevalence of co-authorship and in identifying the style of authorship and the research approaches taken. It was found that of the 362 authors, most of them are single authors at 75.7 and 24.3% were involved in co-authorship. In terms of the types of papers, 72.7% wrote essay or opinion papers, 17.7% wrote articles based on quantitative approaches, 7.7% wrote qualitative articles and 2.2% wrote articles using mixed method approaches. These findings have important implications for research and publication in higher education and research in and on the Pacific Islands, in terms of encouraging collaborative research among researchers and being out in the field to collect data to enable better evidence for education