Kelly BL, Ferreira A.
Beta-amyloid disrupted synaptic vesicle endocytosis in cultured hippocampal neurons.
Neuroscience. 2007 Jun 15;147(1):60-70.
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This interesting study shows that application of synthetic oligomeric Aβ impairs synaptic vesicle endocytosis, likely due to a decrease in dynamin 1 levels. In their discussion, Kelly and Ferreira indicate that their results conflict with a recent report from our lab (Ting et al., 2007), but I believe our results are, in fact, entirely consistent with theirs.
Although we found no difference in total FM dye uptake in neurons overexpressing APP (in contrast to Kelly and Ferreira), our experimental design included 1 minute of dye uptake after the end of the train of action potentials used to trigger vesicle cycling. It has recently been shown that dynamin 1 is not required for the phase of endocytosis after cessation of stimulation, whereas endocytosis during prolonged bouts of stimulation is highly dependent on dynamin 1 (Ferguson et al., 2007). Thus, our dye uptake experiment would not be expected to detect a dynamin 1-mediated endocytic deficit, and suggested only that there was no change in the size of the pool of total cycling vesicles.
When we monitored the rate of destaining during a second train of action potentials, we saw a delayed slowing of dye loss in cells overexpressing APP, which we interpreted as a deficit in endocytosis, in accord with Kelly and Ferreira.
Kelly and Ferreira suggest that the Aβ secreted into our culture medium may have aggregated beyond oligomeric form into less toxic fibrils. This is unlikely because we recorded from cells just 10-24 hours after infection with the virus directing overexpression of APP. In any case, I believe that the slight differences in our protocols for measuring endocytosis can account fully for the apparent discrepancies in our results.
References:Ferguson SM, Brasnjo G, Hayashi M, Wolfel M, Collesi C, Giovedi S, Raimondi A, Gong LW, Ariel P, Paradise S, O'toole E, Flavell R, Cremona O, Miesenbock G, Ryan TA, De Camilli P. A selective activity-dependent requirement for dynamin 1 in synaptic vesicle endocytosis.
Science. 2007 Apr 27;316(5824):570-4.
Ting JT, Kelley BG, Lambert TJ, Cook DG, Sullivan JM. Amyloid precursor protein overexpression depresses excitatory transmission through both presynaptic and postsynaptic mechanisms.
Proc Natl Acad Sci U S A. 2007 Jan 2;104(1):353-8. Epub 2006 Dec 21.