EaeJOURNAL OF EXTRACELLULAR VESICLESPT01: Cellular and Organ Targeting Thursday Poster Session Chairs: Charles Lai; Ikuhiko Nakase Place: Level 3, Hall A 15:306:PT01.Function 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 inside the blood and have an effect on cellular functions in an organ distant from their origins. In neuroscience, systemic circulating factors such as cytokines/chemokines, hormones and metabolites have 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. Procedures: We made use of mouse models to study the effects of EVs from certain cell forms on brain function and behaviour. Mainly because circulating EVs are exceptionally heterogeneous, we PPARβ/δ custom synthesis focused on immunodeficient mice that lack specific lymphocytes (T and B cells). We assessed the changes in their circulating EVs and examined their prospective influence around the corresponding behavioural and neuronal dysregulation. Final results: As expected, immunodeficient mice lack the expression of T and B cell-related markers in the EV containing fractions in the peripheral blood. Immunodeficient mice also displayed social behavioural deficits, accompanying by improve c-Fos immunoreactivity in 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 potential periphery-brain communication by means of EVs below physiological condition. Future research are expected to identify 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 rising interest as drug delivery automobiles. Adenosine A1 receptor (A1R) Agonist custom synthesis However, there is nevertheless a lack of understanding concerning the in vivo fate of exogenous delivered EVs. Noninvasive optical imaging is definitely an important tool to analyse the biodistribution of EVs. At present, just about the most common procedures should be to directly label EVs with fluorescent lipophilic dyes. A significant drawback is the fact that the dye itself in lieu of EVs is detected. Hence, there’s a want for other dyes that overcome these limitations. A brand 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 have 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 have been labelled with ExoGlow-Vivo dye, washed through ultracentrifugation and injected i.v. in post-natal day-.