Inhibition of exosome generation improves MI disrupted SV distribution. a Intraperitoneal injection of GW4869 prevented the synaptic vesicles accumulation at the presynaptic active zone in hippocampal neurons of MI mice. b GW4869 prevented an increase of the total SV number in the synapses in the hippocampi of MI mice. PLevene < 0.0001, one-way ANOVA: F = 19.799, P < 0.0001; Fisher’s PLSD test: Psham: MI < 0.0001, P
MI:GW4869 < 0.0001. n = 20 synapses from 3 mice for each group. c GW4869 redistributed SVs at the active zones of synapses in the nerve terminals of Tg mice. 0 nm shell: PLevene = 0.669, one-way ANOVA: F = 3.424, P = 0.039; Fisher’s PLSD test: P
sham: MI = 0.360, P
MI:GW4869 = 0.012; 50 nm shell: PLevene = 0.016, one-way ANOVA: F = 6.703, P = 0.002; Fisher’s PLSD test: P
sham: MI = 0.003, P
MI:GW4869 = 0.002; 100 nm shell: PLevene < 0.0001, One way ANOVA: F = 14.785, P < 0.0001; Fisher’s PLSD test: P
sham: MI = 0.0001, P
MI:GW4869 < 0.0001. n = 20 synapses from 3 mice for each group. d GW4869 did not affect the length of active zone in hippocampi of MI mice. PLevene = 0.271, one-way ANOVA: F = 1.084, P = 0.345; Fisher’s PLSD test: Psham: MI = 0.185, PMI:GW4869 = 0.885. n = 20 active zones from 3 mice for each group. e Expression of SV related proteins in the hippocampi of MI mice. Left: sample bands of immunoblotting images. Right: statistical analysis of Munc 18, VAMP-2, syntaxin- 1A and SNAP-25. *P < 0.05 (f) Intraperitoneal injection of GW4869 prevented the elevation of miR-1 level in the hippocampi of MI mice, as measured by qRT-PCR. PLevene < 0.0001, one-way ANOVA: F = 7.756, P = 0.011; Fisher’s PLSD test: P
sham: MI = 0.004, P
MI:GW4869 = 0.018. n = 4 animals for each group. g Intraperitoneal injection of GW4869 prevented the decreased SNAP-25 expression in the hippocampi of MI mice, as measured by western blotting. PLevene = 0.265, one-way ANOVA: F = 7.647, P = 0.011; Fisher’s PLSD test: P
sham: MI = 0.010, P
MI:GW4869 = 0.006. n = 4 animals for each group. *P < 0.05 versus WT; #P < 0.05 versus Tg