The study by An and colleagues provides one of the first clues to an ongoing riddle. Why the already very complex pattern of multiple BDNF transcripts is further complicated by attaching the diverse mRNAs to two distinct polyadenylation signals. Making use of very elegant mouse models that were provided by colleagues in the field, the authors provide convincing evidence that mRNA versions with the longer 3'UTR are transported more efficiently into dendrites than those with the short 3'UTR tail.
Given that BDNF is an important mediator of activity-dependent synaptic plasticity, elucidating these subtle details of dendritic BDNF production and action are crucial to better understand the role of this growth factor in dementias such as Alzheimer disease. Several interesting questions arise from their important findings:
1. Data are required to show that regulated release of BDNF is affected selectively in dendrites and not in the soma, as the authors suggest.
2. The lack of dendritic BDNF protein surprisingly has a gain-of-function phenotype (increased number of dendritic...