A8 MICROBIAL ACTIVATION OF INTESTINAL DENDRITIC CELLS IS CRITICAL FOR THE ESTABLISHMENT OF NORMAL BEHAVIOR

Abstract Background Accumulating evidence suggests that gut microbiota affects brain development and its function. It is well known compared with conventional mice (SPF), germ-free (GF) display higher exploratory behavior, which normalizes after bacterial colonization. However, little about the underlying mechanisms first critical steps initiating microbiota-gut-brain communication, lead to establishment of normal behavior. Purpose To investigate role immune system in behavior Method We assessed GF before colonization SPF microbiota, Altered Schaedler Flora (ASF) or single strain E. coli JM83, them mice, using light-dark preference tail suspension tests. Levels brain-derived neurotrophic factor (BDNF) c-Fos expression were measured by immunofluorescence hippocampus amygdala. Colonic gene a NanoString technology. The immunodeficient MyD88-/- Ticam1- SCID used study innate adaptive systems. demonstrate dendritic cells (DCs), we mono-colonization JM83 treated cosalane fingolimod, inhibit DCs activation migration, respectively. Brain levels CD11b, CD11c CD103 as markers was immunofluorescence. Result(s) Compared showed less depressive-like ex-germ-free colonized ASF mono-colonized similar normalization those microbiota. Mono-colonization reduced both BDNF c-fos While induced same change wild-type MyD88-/-Ticam1-/- did not alter their affected multiple genes colon brain, associated immunity neural plasticity. Treatment fingolimod prevented behavioral changes colonization, paralleled absence CD11b+CD103+CD11c+ otherwise found high numbers control absent mice. Conclusion(s) system, through migration intestinal into initiates neuro-immune signaling within gut-brain axis leads Our findings may impact several psychiatric conditions, altered has been implicated. Please acknowledge all funding agencies checking applicable boxes below CIHR, Other indicate your source funding; Balsam Family Foundation Disclosure Interest None Declared