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In the paper on mature BDNF vs proBDNF in synapse competition by Je et al., PNAS, 109:15924-9. The authors suggest that mature BDNF promotes synapse stabilization.

1)    Suggest one general mechanism to explain how BDNF might stabilize a synapse. In your explanation, state one specific hypothesis that you could experimentally test.

2)    Describe one experiment to test your hypothesis.

3)    You decide to perform a similar experiment with mammalian cells, using rat neurons and muscle cells. Similar to the Xenopus results (Fig.1 of Je et al.), you find that the activated synapse is stablilized, but the inactive one withdraws. Moreover, you find that adding a pan-matrix metalloprotease (MMP) inhibitor induces the retraction of both axons, even the active one (similar to Fig. 4 of Je et al.). You also find that there is no retraction of the inactive axon when using neurons from p75-/- mice. However, unlike the Je et al. results, you cannot detect any proBDNF released, and when you use an antibody that blocks binding of proBDNF to p75, there is no effect (the active synapse remains and the inactive one withdraws). Provide a possible explanation for these findings.