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Fig. 10 | Molecular Neurodegeneration

Fig. 10

From: Dynamic presenilin 1 and synaptotagmin 1 interaction modulates exocytosis and amyloid β production

Fig. 10

Syt1 overexpression in vivo increases PS1-Syt1 interactions and promotes open PS1 conformation in mouse brain. a Schematic representation of the experimental design. Bilateral injection of AAV2/8-hSyn1. Syt1-V5 or empty plasmid to the contralateral hemisphere was performed. One month after the injections the brains were dissected and subjected to immunofluorescence analysis. b The fluorescent images demonstrate successful expression of Syt1-V5 in mouse brain one month after the AAV2/8-hSyn1. Syt1-V5 injection. The tissue was immunostained with anti-V5 antibody and corresponding Cy3-conjugated secondary antibody. c, d The bar graphs present FLIM assays of the PS1-Syt1 interactions and PS1 conformation in mouse hippocampi injected with AAV2/8-hSyn1. Syt1-V5 or empty vector as a control. The tissue was immunostained with anti-PS1 NT and anti-Syt1 for the PS1-Syt1 interaction assay, or anti-PS1 NT and anti-PS1 loop antibodies for the PS1 conformation assay, followed by respective fluorescently labeled secondary antibodies. There is a significant increase in the PS1-Syt1 binding and a shift towards protective “open” conformation of PS1 in the hemispheres transduced with AAV2/8-hSyn1. Syt1-V5. The data are presented as mean ± SEM, n = 721-723 neurons for PS1-Syt1 interaction and n = 573-586 for PS1 conformation were analyzed in 5 mice. Statistical significance was determined using Mann-Whitney’s U-test, ***p < 0.001. The fluorescence lifetimes and corresponding FRET efficiency values are shown in the Additional file 1

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