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Journal: Cell Genomics
Article Title: ABCA7-dependent induction of neuropeptide Y is required for synaptic resilience in Alzheimer’s disease through BDNF/NGFR signaling
doi: 10.1016/j.xgen.2024.100642
Figure Lengend Snippet: ABCA7 regulates synaptic integrity and astroglial proliferation through BDNF (A) Experimental setup for investigating the biological relevance of NPY to abca7 function and amyloid-induced alterations in synaptic integrity, microglial activity, and astroglial proliferation. (B) Immunofluorescence for SV2 + L-plastin and GS + PCNA with DAPI counterstains in abca7 +/− + PBS, abca7 +/− + Aβ42, abca7 +/− + NPY, and abca7 +/− + Aβ42 + NPY brains. (C) Quantification for number of SV2-positive synaptic puncta, L-plastin-positive microglia, and GS/PCNA double-positive proliferating astroglia. n = 4 animals from both sexes and ≥20 brain sections per group. One-way ANOVA with Tukey’s multiple comparison test was used for statistical analyses. No comparison bar indicates no significance. (D) BDNF immunoreactivity in wild-type and abca7 knockout zebrafish with and without Aβ42. Aβ42 induced BDNF (red) in wild-type animals but not in abca7 knockout. Injection of NPY with or without Aβ42 restores the induced BDNF expression levels. Non-parametric Kolmogorov-Smirnov test comparing cumulative distributions and one-way ANOVA with Tukey’s multiple comparison test were used for statistical analyses. (E) Immunofluorescence for SV2 and L-plastin with DAPI counterstain in abca7 +/− + Aβ42 + PBS and abca7 +/− + Aβ42 + BDNF zebrafish brains. Quantification for the number of SV2-positive synaptic puncta and the number of L-plastin-positive microglia. Non-parametric Kolmogorov-Smirnov test comparing cumulative distributions was used for statistical analyses. BDNF rescues synaptic integrity changes in abca7 +/− knockout similar to NPY. n = 4 animals from both sexes, with 18 brain sections per group. ∗ p < 0.0332, ∗∗ p < 0.0021, ∗∗∗ p < 0.0002, ∗∗∗∗ p < 0.0001; not significant (ns), p > 0.0332. Scale bars, 50 μm. See also Figures S1 and , and , and Table S1 .
Article Snippet: SV2 , Developmental Studies Hybridoma Bank - DSHB , Cat# SV2; RRID: AB_2315387.
Techniques: Activity Assay, Immunofluorescence, Comparison, Knock-Out, Injection, Expressing