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Fig. 5 | Acta Neuropathologica Communications

Fig. 5

From: Attenuation of neuroinflammation reverses Adriamycin-induced cognitive impairments

Fig. 5

Extracellular vesicles (EV) isolated from human induced pluripotent stem cell (iPSC)-derived microglia (iMG) prevent the development of Adriamycin-induced cognitive dysfunction. a Schematic of the experimental design: adult wild type (C57BL/6 J) male mice received chronic Adriamycin (ADR) treatment (2 mg/kg, i.p.) once weekly for 4 weeks. One week after the last ADR injection animal received intravenous (retro orbital vein) injections of iMG-EV (1.36 × 107 EVs per injection in 50 μL volume, once weekly for 4 weeks). One week after iMG-EV injections, mice were administered novel object recognition (NOR) and fear extinction memory (FE) tasks. After completion of cognitive testing, brains were harvested for immunohistochemical analyses. b Chronic ADR treatment caused a significantly reduced discrimination index (DI) on the NOR task (**, P < 0.002 compared to Controls). ADR-treated mice receiving iMG-EV injections (ADR + iMG-EV) show a significant improvement in performance on the NOR task (*, P < 0.01 compared to the ADR group). c Neither treatment with ADR nor iMG-EV impaired the acquisition of conditioned fear as indicated by elevated freezing following a series of 3 tone-shock pairings (0.6 mA, T1-T3). 24-h after the conditioning phase, fear extinction training was administered every 24-h (20 tones) for 2 days. All mice showed a gradual decrease in freezing behavior (Day 1–2), however, ADR-treated mice spent a significantly higher percent time in freezing compared to controls (*, P’s < 0.01). c1 24 h after extinction training, Control and ADR + iMG-EV mice showed abolished fear memory compared to ADR-treated mice receiving vehicle (*, P < 0.01; **, P < 0.002 compared to ADR group). Data are presented as mean ± SEM (N = 8 mice per group). P values were derived from ANOVA and Bonferroni’s post hoc test

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