EaeJOURNAL OF EXTRACELLULAR VESICLESPT01: Cellular and Organ Targeting Thursday Poster Session Chairs: Charles Lai; Ikuhiko Nakase Location: Level three, Hall A 15:306:PT01.Role of circulating extracellular vesicles in brain function and behaviour Eisuke Dohi, Indigo Rose, Takashi Imai, Rei Mitani, Eric Choi, Dillon Muth, Zhaohao Liao, Kenneth Witwer and Shinichi Kano Johns Hopkins University School of Medicine, Baltimore, USAPT01.In vivo tracking and monitoring of extracellular vesicles with a new non-lipophilic dye Sam Noppena, Gareth R Willisb, Antonios Fikatasa, Archana Guptac, Amirali Afsharic, 5-HT7 Receptor Antagonist MedChemExpress Christophe Pannecouquea and Dominique ScholsaaIntroduction: Accumulating evidence suggests that extracellular vesicles (EVs) circulate within the blood and impact cellular functions in an organ distant from their origins. In neuroscience, systemic circulating components such as cytokines/chemokines, hormones and metabolites have already been shown to modulate brain function and behaviour. They’re also utilized as biomarkers to reflect brain disease status. Nonetheless, it remains unclear whether or not circulating EVs modulate brain function and behaviour. Procedures: We utilized mouse models to study the effects of EVs from particular cell sorts on brain function and behaviour. Due to the fact circulating EVs are very heterogeneous, we focused on NF-κB1/p50 Molecular Weight immunodeficient mice that lack certain lymphocytes (T and B cells). We assessed the alterations in their circulating EVs and examined their prospective influence around the corresponding behavioural and neuronal dysregulation. Benefits: As expected, immunodeficient mice lack the expression of T and B cell-related markers inside the EV containing fractions from the peripheral blood. Immunodeficient mice also displayed social behavioural deficits, accompanying by boost c-Fos immunoreactivity in the excitatory neurons inside the medial prefrontal cortex (mPFC). Notably, transfer of splenocytes from wild-type (WT) rescued the behavioural deficits, serum EVs and brain c-Fos expression patterns in immunodeficient mice. Further analysis on the molecular mechanisms is in progress. Summary/Conclusion: Our study has revealed a prospective periphery-brain communication by way of EVs beneath physiological condition. Future research are expected to recognize the cellular targets of circulating EVs and their ascending routes inside the brain. Funding: NIMH R01.Laboratory of Virology and Chemotherapy, Rega Institute, KU Leuven, Leuven, Belgium; bDepartment of Pediatrics, Harvard Medical College, MA, Boston, USA; cSystem Biosciences (SBI), Palo Alto, CA, USAIntroduction: Extracellular vesicles (EVs) are gaining escalating interest as drug delivery autos. Having said that, there’s still a lack of know-how in regards to the in vivo fate of exogenous delivered EVs. Noninvasive optical imaging is definitely an critical tool to analyse the biodistribution of EVs. At the moment, one of the most preferred tactics is always to directly label EVs with fluorescent lipophilic dyes. A major drawback is the fact that the dye itself instead of EVs is detected. Hence, there’s a have to have for other dyes that overcome these limitations. A new non-lipophilic near infrared (NIR) dye, ExoGlow-Vivo (SBI), was tested in vivo in mice. Approaches: EVs from human PBMC, HEK and MCF7 cells had been labelled with ExoGlow-Vivo, precipitated with Exoquick-TC (SBI) and injected intravenously (i.v.) in adult SCID mice. Human mesenchymal stem cell (MSC)-derived EVs had been labelled with ExoGlow-Vivo dye, washed by way of ultracentrifugation and injected i.v. in post-natal day-.