BDNF stimulates the retrograde pathway for axonal autophagy

ABSTRACT Autophagy is a lysosomal degradative pathway important for neuronal development, function, and survival. But how autophagy in axons is regulated by neurotrophins to impact neuronal viability and function is poorly understood. Here, we investigate the regulation of axonal autophagy by the neurotrophin BDNF, and elucidate whether autophagosomes carry BDNF-mediated signaling information. We find that BDNF induces autophagic flux in primary neurons by stimulating the retrograde pathway for autophagy in axons. We observed an increase in autophagosome density and retrograde flux in axons, and a corresponding increase in autophagosome density in the soma. However, we find little evidence of autophagosomes co-migrating with BDNF. In contrast, BDNF effectively engages its cognate receptor TrkB to undergo retrograde transport in the axon. These compartments, however, are distinct from LC3-positive autophagic organelles in the axon. Together, we find that BDNF stimulates autophagy in the axon, but retrograde autophagosomes do not appear to carry neurotrophin-based signaling information. Thus, BDNF likely stimulates autophagy as a consequence of BDNF-induced processes that require canonical roles for autophagy in degradation, rather than unconventional roles in neurotrophin signaling.