BDNF high expression in hippocampus ameliorated memory impairment in rTg4510 mice (IMAGE)
Caption
(A) Timeline for experiments in rTg4510 mice. WT littermate, n = 20; AAVT42-GFP, n = 16; AAVT42-BDNF, n = 24.
(B) Analysis of open field test, age was 7–8 months. Left: total traveled distance. WT littermate: 152.6 ± 4.9 m; AAVT42-GFP: 291.1 ± 43.6 m; AAVT42-BDNF: 296.5 ± 34.0 m ∗∗∗P = 8.0 × 10−4 for WT littermate vs. AAVT42-GFP, P = 0.93 for AAVT42-GFP vs. AAVT42-BDNF, ∗∗∗P = 1.0 × 10−4 for WT littermate vs. AAVT42-BDNF. Left: time spent in the center area. WT littermate: 222.4 ± 12.05 s; AAVT42-GFP:136.7 ± 22.85 s; AAVT42-BDNF:134.8 ± 21.54 s ∗∗P = 4.3 × 10−3 for WT littermate vs. AAVT42-GFP, P = 0.91 for AAVT42-GFP vs. AAVT42-BDNF, ∗∗P = 1.0 × 10−3 for WT littermate vs. AAVT42-BDNF
(C) Percentage of spontaneous alternation in Y maze. WT littermate, n = 20; AAVT42-GFP, n = 13; AAVT42-BDNF, n = 21. WT littermate: 63.24% ± 1.77%; AAVT42-GFP: 50.10% ± 3.49%; AAVT42-BDNF: 62.93% ± 2.93%. ∗∗P = 2.2 × 10−3 for WT littermate vs. AAVT42-GFP, ∗∗P = 2.6 × 10−3 for AAVT42-GFP vs. AAVT42-BDNF, P = 0.93 for WT littermate vs. AAVT42-BDNF
(D) Analysis of Morris water maze. Escape latency of cohorts each day during Morris water maze training. WT littermate, n = 14; AAVT42-GFP, n = 9; AAVT42-BDNF, n = 10. On the 5th day, WT littermate: 11.70 ± 1.53 s; AAVT42-GFP: 39.39 ± 5.11 s; AAVT42-BDNF: 33.18 ± 5.78 s ∗∗∗P = 5.0 × 10−4 for WT littermate vs. AAVT42-GFP, P = 0.43 for AAVT42-GFP vs. AAVT42-BDNF, ∗∗P = 4.7 × 10−3 for WT littermate vs. AAVT42-BDNF. For probe tests, quantification of time spent in the target quadrant zone (WT littermate: 24.73 ± 1.70 s; AAVT42-GFP: 9.66 ± 2.09 s; AAVT42-BDNF: 19.51 ± 3.42 s ∗∗∗∗P < 1.0 × 10−4 for WT littermate vs. AAVT42-GFP, P = 0.066 for AAVT42-GFP vs. AAVT42-BDNF, ∗P = 0.033 for WT littermate vs. AAVT42-BDNF) and target quadrant visit frequency (WT littermate: 26.50 ± 2.82; AAVT42-GFP: 17.56 ± 6.62; AAVT42-BDNF: 31.60 ± 6.94)
(E) Percentage of freezing time during three consecutive stimuli. At 3rd stimulus, freezing ratio of WT littermate: 67.674 ± 6.397 %, n = 11; AAVT42-GFP = 26.744% ± 11.528%, n = 8; AAVT42-BDNF = 33.092% ± 10.068%, n = 6. ∗∗P = 9.0 × 10−3 for WT littermate vs. AAVT42-GFP, P = 0.69 for AAVT42-GFP vs. AAVT42-BDNF, ∗P = 0.017 for WT littermate vs. AAVT42-BDNF. The freezing ratio during contextual test: WT littermate, 48.02% ± 8.57%; AAVT42-GFP, 14.75% ± 4.38%; AAVT42-BDNF, 50.64% ± 13.71%. ∗P = 0.011 for WT littermate vs. AAVT42-GFP, ∗P = 0.018 for AAVT42-GFP vs. AAVT42-BDNF, P = 0.84 for WT littermate vs. AAVT42-BDNF. The freezing ratio during the conditioned-cue test: WT littermate, 65.46% ± 6.43%; AAVT42-GFP, 61.67% ± 7.56%; AAVT42-BDNF, 64.53% ± 7.03% (F, G) Representative images of NeuN and MAP-2 immunostaining in the CA1 region of the hippocampus, age was around 12 months (H) Quantification of the thickness of SPy layer of NeuN fluorescence in CA1 region. n = 3 for each group. WT littermate: 65.40 ± 1.15 μm; AAVT42-GFP, 27.70 ± 3.12 μm; AAVT42-BDNF, 49.40 ± 4.36 μm ∗∗∗∗P < 1.0 × 10−4 WT littermate vs. AAVT42-GFP, ∗∗∗P = 3.0 × 10−4 AAVT42-GFP vs. AAVT42-BDNF, ∗∗P = 5.1 × 10−3 for WT littermate vs. AAVT42-BDNF. Each point represents one half of the coronal hippocampus (I–K) Immunofluorescence of GFAP for astrocytes in CA1 region (quantification of mean fluorescence intensity in Figure 4J. WT littermate: 47.47 ± 0.87, n = 3; AAVT42-GFP: 57.61 ± 3.86, n = 3; AAVT42-BDNF: 59.05 ± 1.19, n = 4. ∗∗P = 4.1 × 10−3 for WT littermate vs. AAVT42-GFP, P = 0.62 for AAVT42-GFP vs. AAVT42-BDNF, ∗∗∗P = 6.0 × 10−4 for WT littermate vs. AAVT42-BDNF), and Iba1 for microglia in CA1 region (quantification of mean fluorescence intensity in Figure 4K. WT littermate: 41.56 ± 0.36, n = 3; AAVT42-GFP: 62.59 ± 0.79, n = 3; AAVT42-BDNF: 60.69 ± 0.59, n = 4. ∗∗∗P = 4.0 × 10−4 for WT littermate vs. AAVT42-GFP, P = 0.27 for AAVT42-GFP vs. AAVT42-BDNF, ∗∗P = 7.8 × 10−3 for WT littermate vs. AAVT42-BDNF) (L) Representative images of phosphorylated Tau (AT8) DAB staining in the hippocampus (M) Quantification of phosphorylated Tau in the hippocampus, mice age of 9–12 months. AAVT42-GFP: 0.45 ± 0.023, n = 5; AAVT42-BDNF: 0.48 ± 0.014, n = 7. Each mouse was quantified in dentate gyrus and CA3 regions. SO, stratum oriens; SR, stratum radiatum; SPy, stratum pyramidale.
Credit
Siqi Tang, Wenshu Luo, Shihao Wu, Meng Yuan, Jiashuo Wen, Guoshen Zhong, Leshan Shen, Wei Jiang, Cheng Cheng, Xia Wu, Xiao Xiao
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