Figure 4: Rescue of the impaired spine development and behavioural abnormalities in ARHGAP33 KO mice via TrkB activation in adulthood. | Nature Communications

Figure 4: Rescue of the impaired spine development and behavioural abnormalities in ARHGAP33 KO mice via TrkB activation in adulthood.

From: Emerging roles of ARHGAP33 in intracellular trafficking of TrkB and pathophysiology of neuropsychiatric disorders

Figure 4

(a) Activation of TrkB by 7,8-DHF injection (12.5 mg kg−1). TrkB-immunoprecipitates and hippocampal lysates were immunoblotted with the indicated antibodies. Representative blots (upper) and quantification of phospho-TrkB levels (lower; each n=9, corrected P=0.0014, Mann–Whitney U-test with the Ryan’s correction). The pY-TrkB levels of vehicle-KO, DHF-WT and DHF-KO were normalized to that of vehicle-WT (The averaged vehicle-WT value was set to 100%). Bars show median values. (b) Rescue of the decreased number of spines in ARHGAP33 KO neurons after 2 weeks of daily treatment with 7,8-DHF. Examples of dentate granule Golgi staining (upper). Scale bars, 10 μm. Quantification of the total spine density and the percentage of mature spines (vehicle-WT, n=29 cells, vehicle-KO, n=30, DHF-WT, n=28 cells, DHF-KO, n=31 cells, each n=4 mice; spine density, F1,114=19.7, P=2.1 × 10−5, two-way ANOVA; P=9.7 × 10−10 (vehicle-WT versus vehicle-KO), P=3.6 × 10−10 (vehicle-KO versus DHF-KO), Tukey–Kramer post hoc tests; mature spine density, F1,114=83.7, P=2.6 × 10−15, two-way ANOVA; P=7.3 × 10−26 (vehicle-WT versus vehicle-KO), P=4.9 × 10−21 (vehicle-KO versus DHF-KO), Tukey–Kramer post hoc tests; lower). Bars show mean values. (c) Rescue of the impaired working memory in ARHGAP33 KO mice during the Y-maze test after treatment with 7,8-DHF (vehicle-WT, n=12, vehicle-KO, n=16, DHF-WT, n=16, DHF-KO, n=15, DHF treatment × genotype interaction, F1,55=4.60, P=0.036, two-way ANOVA; P=4.6 × 10−3 (vehicle-WT versus vehicle-KO), P=1.1 × 10−3 (vehicle-KO versus DHF-KO), Tukey–Kramer post hoc tests). Bars show mean values. (d) Rescue of the impaired open-field habituation in ARHGAP33 KO mice after treatment with 7,8-DHF on the test day (day 4; vehicle-WT, n=20, vehicle-KO, n=16, DHF-WT, n=17, DHF-KO, n=14, corrected P=0.0052 (vehicle-WT versus vehicle-KO), corrected P=0.035 (vehicle-KO versus DHF-KO), Mann–Whitney U-test with the Ryan’s correction). *P<0.05. NS, not significant. Bars show median values.

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