title: BDNF and its pro-peptide are stored in presynaptic dense core vesicles in brain neurons.
abstract: Although brain-derived neurotrophic factor (BDNF) regulates numerous and complex biological processes including memory retention, its extremely low levels in the mature central nervous system have greatly complicated attempts to reliably localize it. Using rigorous specificity controls, we found that antibodies reacting either with BDNF or its pro-peptide both stained large dense core vesicles in excitatory presynaptic terminals of the adult mouse hippocampus. Both moieties were ~10-fold more abundant than pro-BDNF. The lack of postsynaptic localization was confirmed in Bassoon mutants, a seizure-prone mouse line exhibiting markedly elevated levels of BDNF. These findings challenge previous conclusions based on work with cultured neurons, which suggested activity-dependent dendritic synthesis and release of BDNF. They instead provide an ultrastructural basis for an anterograde mode of action of BDNF, contrasting with the long-established retrograde model derived from experiments with nerve growth factor in the peripheral nervous system.
authors.affiliation: Department of Neuroanatomy, Institute of Anatomy and Cell Biology, Albert-Ludwigs-University Freiburg, 79104 Freiburg, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Dieni
authors.forename: Tomoya
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Martijn
authors.initials: M
authors.lastname: Dekkers
authors.forename: Stefanie
authors.initials: S
authors.lastname: Rauskolb
authors.forename: Mihai S
authors.initials: MS
authors.lastname: Ionescu
authors.forename: Ruben
authors.initials: R
authors.lastname: Deogracias
authors.forename: Eckart D
authors.initials: ED
authors.lastname: Gundelfinger
authors.forename: Masami
authors.initials: M
authors.lastname: Kojima
authors.forename: Sigrun
authors.initials: S
authors.lastname: Nestel
authors.forename: Michael
authors.initials: M
authors.lastname: Frotscher
authors.forename: Yves-Alain
authors.initials: YA
authors.lastname: Barde
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D009474:Neurons / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000502:physiology*; D011498:Protein Precursors / Q000378:metabolism; D022142:Secretory Vesicles / Q000737:chemistry / Q000378:metabolism*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D011498:Protein Precursors; C426674:brain-derived neurotrophic factor precursor