Amyloid-Beta Induced Changes in Vesicular Transport of BDNF in Hippocampal Neurons

Figure 1

Transport dynamics of BDNF-containing vesicles in hippocampal neurons of 5xFAD mice. Dissociated hippocampal neurons of transgenic mice with five familial Alzheimer’s disease mutations (5xFAD) and wild-type littermates were transfected at 10 DIV with fluorescently labeled BDNF. The dynamic behavior of BDNF-containing vesicles was analyzed by live cell imaging. (a) Representative picture of a hippocampal neuron transfected with BDNF-mCherry. (b) Boxed area from (a) at higher magnification and at different time points of time-lapse recording. Red and yellow circles mark BDNF-containing vesicles showing a directional movement. Red circle marks a vesicle which moves in anterograde direction from the soma to distal part of the neurite, while yellow circle marks a vesicle which moves in retrograde direction from distal part of the neurite to the soma of the neuron. Green circle marks a vesicle which was immobile during observation. (c) Bar diagram showing the mean motility of BDNF-containing vesicles in hippocampal neurons of 5xFAD mice compared to wild-type littermates. Note that the motility of BDNF-containing vesicles was significantly reduced in hippocampal neurons from 5xFAD mice compared to wild-type littermates. (d) Bar diagram indicates the percentage of immobile BDNF-containing vesicles. Note that there are significantly more immobile vesicles in neurons of transgenic animals compared to wild-type littermates. (e) Transport characteristics of mobile anterogradely directed BDNF-containing vesicles. Bar diagrams show motional properties of BDNF-containing vesicles as indicated. The overall average speed and the average speed during motion, run length, and stopping frequency of BDNF-containing vesicles were significantly changed in neurons of transgenic animals compared to wild-type littermates. (f) Motional properties of retrogradely directed BDNF-containing vesicles. All motional properties of BDNF-containing vesicles moving in retrograde direction were significantly changed in neurons of transgenic animals compared to wild-type littermates. (, , ; one-way ANOVA). Error bars represent SEM.

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