EaeJOURNAL OF EXTRACELLULAR VESICLESPT01: Cellular and Organ Targeting Thursday Poster Session Chairs: Charles Lai; Ikuhiko Nakase Place: 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, Christophe Pannecouquea and Dominique ScholsaaIntroduction: Accumulating proof suggests that extracellular vesicles (EVs) circulate within the blood and influence cellular functions in an organ distant from their origins. In neuroscience, systemic circulating variables like cytokines/chemokines, hormones and metabolites have already been shown to modulate brain function and behaviour. They are also utilized as biomarkers to reflect brain disease status. Nonetheless, it remains unclear irrespective of whether circulating EVs modulate brain function and behaviour. Methods: We utilized mouse models to study the effects of EVs from certain cell forms on brain function and behaviour. Simply because circulating EVs are exceptionally heterogeneous, we focused on immunodeficient mice that lack distinct lymphocytes (T and B cells). We assessed the changes in their circulating EVs and examined their possible influence on 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 in the peripheral blood. Immunodeficient mice also displayed social behavioural deficits, accompanying by improve c-Fos immunoreactivity inside the excitatory neurons in 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 via EVs below physiological condition. Future studies are essential to recognize the cellular targets of circulating EVs and their ascending routes in the brain. Funding: NIMH R01.Laboratory of Virology and Chemotherapy, Rega Institute, KU Leuven, Leuven, Belgium; bDepartment of Pediatrics, Harvard Healthcare School, MA, Boston, USA; cSystem Biosciences (SBI), Palo Alto, CA, USAIntroduction: Extracellular vesicles (EVs) are gaining escalating interest as drug delivery vehicles. Having said that, there’s nonetheless a lack of knowledge regarding the in vivo fate of exogenous delivered EVs. Noninvasive PDE6 Formulation optical imaging is definitely an vital tool to analyse the biodistribution of EVs. At present, one of the most well-known strategies is always to directly label EVs with fluorescent lipophilic dyes. A significant drawback is that the dye itself instead of EVs is detected. Therefore, there is a need for other dyes that overcome these limitations. A new non-lipophilic near infrared (NIR) dye, ExoGlow-Vivo (SBI), was tested in vivo in mice. Strategies: EVs from human PBMC, HEK and MCF7 cells were labelled with ExoGlow-Vivo, S1PR4 Source precipitated with Exoquick-TC (SBI) and injected intravenously (i.v.) in adult SCID mice. Human mesenchymal stem cell (MSC)-derived EVs have been labelled with ExoGlow-Vivo dye, washed via ultracentrifugation and injected i.v. in post-natal day-.