PMID- 16957779 OWN - NLM STAT- MEDLINE DCOM- 20061024 LR - 20181113 IS - 0261-4189 (Print) IS - 1460-2075 (Electronic) IS - 0261-4189 (Linking) VI - 25 IP - 18 DP - 2006 Sep 20 TI - Hippocampal neurons recycle BDNF for activity-dependent secretion and LTP maintenance. PG - 4372-80 AB - Regulation of brain-derived neurotrophic factor (BDNF) secretion plays a critical role in long-term potentiation (LTP). It is generally thought that the supply for this secretion is newly synthesized BDNF targeted to the synapse. Here we provide evidence that hippocampal neurons additionally recycle BDNF for activity-dependent secretion. Exogenously applied BDNF is internalized by cultured neurons and rapidly becomes available for activity-dependent secretion, which is controlled by the same mechanisms that regulate the secretion of newly synthesized BDNF. Moreover, BDNF recycling replaced the new synthesis pathway in mediating the maintenance of LTP in hippocampal slices: the late phase LTP, which is abolished by protein synthesis inhibition, was rescued in slices preincubated with BDNF. Thus, endocytosed BDNF is fed back to the activity-dependent releasable pool required for LTP maintenance. FAU - Santi, Spartaco AU - Santi S AD - CNR-ITOI/ISMN, Bologna, Italy. FAU - Cappello, Silvia AU - Cappello S FAU - Riccio, Massimo AU - Riccio M FAU - Bergami, Matteo AU - Bergami M FAU - Aicardi, Giorgio AU - Aicardi G FAU - Schenk, Ursula AU - Schenk U FAU - Matteoli, Michela AU - Matteoli M FAU - Canossa, Marco AU - Canossa M LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20060907 PL - England TA - EMBO J JT - The EMBO journal JID - 8208664 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Protein Synthesis Inhibitors) RN - 6C74YM2NGI (Anisomycin) RN - EC 2.7.10.1 (Receptor, trkB) SB - IM MH - Animals MH - Anisomycin/pharmacology MH - Brain-Derived Neurotrophic Factor/*metabolism/pharmacology MH - Cells, Cultured MH - Endocytosis MH - Hippocampus/drug effects/*metabolism MH - In Vitro Techniques MH - Long-Term Potentiation/drug effects/*physiology MH - Male MH - Microscopy, Electron MH - Neurons/drug effects/metabolism MH - Protein Synthesis Inhibitors/pharmacology MH - Rats MH - Rats, Sprague-Dawley MH - Receptor, trkB/metabolism PMC - PMC1570444 EDAT- 2006/09/08 09:00 MHDA- 2006/10/25 09:00 PMCR- 2007/09/20 CRDT- 2006/09/08 09:00 PHST- 2006/02/27 00:00 [received] PHST- 2006/08/02 00:00 [accepted] PHST- 2006/09/08 09:00 [pubmed] PHST- 2006/10/25 09:00 [medline] PHST- 2006/09/08 09:00 [entrez] PHST- 2007/09/20 00:00 [pmc-release] AID - 7601303 [pii] AID - 10.1038/sj.emboj.7601303 [doi] PST - ppublish SO - EMBO J. 2006 Sep 20;25(18):4372-80. doi: 10.1038/sj.emboj.7601303. Epub 2006 Sep 7.