Excessive Astrocyte-Derived Neurotrophin-3 Contributes to the Abnormal Neuronal Dendritic Development in a Mouse Model of Fragile X Syndrome
Figure 9
Down-regulation astrocyte-derived NT-3 in vivo reversed the trace fear memory of Fmr1 KO mice.
A, ACC section (left upper) showing bilateral GFP-expressing astrocytes 10 days after microinjection. Scale bar, 500 µm; insert: scale bar, 50 µm. Right column showing cannula tip placements in the ACC of WT sham (solid circles), KO sham (open circles), KO mice injected with negative shRNA infected WT astrocytes (solid triangles) or NT-3 shRNA infected KO astrocytes (open triangles). B, ACC microinjection with negative shRNA infected WT astrocytes and si-508 shRNA infected KO astrocytes showed significantly reduced freezing time as compared to KO sham mice during trace fear condition. n = 6 mice in WT and KO sham group, n = 5 in KO mice injected with negative shRNA infected WT astrocytes and si-508 shRNA infected KO astrocytes group. C, Transplantation of negative shRNA infected WT astrocytes and si-508 shRNA infected KO astrocytes in KO mice exhibit reduced average freezing within the intertrial intervals of the training and testing sessions. n = 6 mice in WT and KO sham group, n = 5 in KO mice injected with negative shRNA infected WT astrocytes and si-508 shRNA infected KO astrocytes group. *P<0.05, ** P<0.01 compared with the WT sham; #P<0.05, ##P<0.01compared with the KO sham. D, Levels of the NT-3 were significantly decreased in the ACC of KO mice after local injection of negative shRNA infected WT astrocytes and si-508 shRNA infected KO astrocytes. n = 6 mice in each group. *P<0.05 compared with the WT sham; #P<0.05 compared with the KO sham.