Table 1.
Somato-dendritic release of BDNF
| Site | Ref. | Species / type of preparation | Method | Release stimulus | Pharmacology / molecular mechanism / time course of BDNF release |
|---|---|---|---|---|---|
| Somato-dendritic release of BDNF | |||||
| Wilson Horch et al. 1999 | Organotypic slices | Postsynaptic BDNF-myc; TrkB-IgG | postsynaptic BDNF overexpression alters density and stability of spines | ||
| Hartmann et al. 2001 | Rat; hippocampal cultures |
Live cell imaging, BDNF-GFP |
Elevated extracellular K+ |
Reduced by: TTX; 0mM Ca2+; 2 mM Cd2+/2 mM Ni2+; Not affecetd: APV, DNQX, LY 341495 (mGluR antagonist) |
|
| HFS | Reduced by: APV, DNQX | ||||
| Kojima et al. 2001 | Rat; hippocampal cultures | Live cell imaging BDNF-GFP | Elevated extracellular K+ | Reduced by: TTX | |
| Brigadski et al. 2005 | Rat; hippocampal cultures | Live cell imaging BDNF-GFP | Elevated extracellular K+ |
Dependency of release kinetics on intragranular pH Comparison of neurotrophin and neurotransmitter release kinetics |
|
| Arancibia et al. 2007 | Adult rat; push pull perfusion + ELISA | ELISA | Intra supraoptic nucleus osmotic stimulation (1M NaCl for 10 min) | In vivo measurement of endogenous BDNF secretion | |
| Kolarow et al. 2007 | Rat; hippocampal cultures | Live cell imaging BDNF-GFP | Elevated extracellular K+ |
Kiss and run fusion events Reduced by: 0 mM Ca2+; nifedipine; thapsigargine; CPA; ryanodine; KN-93; KN-62; Rp-cAMP Not affected by: TTX; KN-92; 8-Br-cAMP; K252a |
|
| Kuczewski et al. 2008 | Rat; hippocampal cultures | Live cell imaging BDNF-GFP | Depolarizations |
Reduced by: GDPβS; Cd2+ Not affected by: QX314 (Na+ channel blocker) |
|
| bAP (8 b-APs at 5 Hz) |
Reduced by: QX314 (Na+ channel blocker); Cd2+ Not affected by: thapsigargine |
||||
| 4-AP (10 min - blocker of Kv1) | Reduced by: NBQX +APV + bicuculline; TTX | ||||
| Dean et al. 2009 |
Rat: E18-20 Mice: P1-3; neuronal cultures |
Live cell imaging BDNF-pHluorin | Elevated extracellular K+ |
Increased after syt-IV knockout; Reduced after syt-IV overexpression Dendritic BDNF release regulates EPSC amplitude |
|
| Fiorentino et al. 2009 | Rat; hippocampal culture | Live cell imaging BDNF-GFP | Baclofen (10μM for 500sec - significant after 5 min application) |
Reduced by: CGP55845 (GABAB-receptor antagonist); Cd2+; Not affected by: NBQX, APV, bicuculline |
|
| Matsuda et al. 2009 | Rat E18-20, neuronal cultures | Live cell imaging BDNF-GFP | HFS field stimulation |
Reduced by: CNQX, APV; CNQX; APV; nimodipine; Cd2+ Not affected by: bafilomycin; dynasore; K252a |
|
| Loose patch stimulation |
Reduced by: nimodipine Not affected by:CNQX + APV; CNQX; APV |
||||
| TBS | Highest efficacy of BDNF release | ||||
| Wit et al. 2009 | Mouse; cortical culture; | Live cell imaging BDNF-sp-pHluorin | Elevated extracellular K+ | Transient and persistent release (deposit) | |
| Xia et al. 2009 | Rat; Hippocampal Cultures | Live cell imaging BDNF-GFP | Elevated extracellular K+ |
Kiss and run fusion events; Release probability in soma is higher than in neurites; Onset of release in soma is delayed in neurites compared to soma Blocked by verapamil (L-Type VGCC) Not affected by conotoxin (N/Q-Type); agatoxin (P-type) |
|
| Yang et al. 2009 | Xenopus; neuron myocte coculture | selective knockdown of BDNF | Repetitive depolarization of myocyte | Transsynaptic action of proBDNF ➔ p75 activation ➔ synaptic retraction | |
| Jakawich et al. 2010 | Rat; hippocampal cultures | TrkB-IgG; BDNF knockdown | Inhibition of AMPAR (3h) | Transcription dependent postsynaptic BDNF release mediates presynaptic increase in mEPSC frequency | |
| Waterhouse et al. 2012 | Mouse; hippocampal cultures | Dendritic myc-IR | potassium | long 3′ UTR controls dendritic localization of BDNF mRNA | |
| Adachi et al. 2013 | Rat; cortical cultures and acute cortical slices |
BDNF-IR ELISA |
Basal secretion |
Reduced by PCP (1μM for 6h) (NMDAR blocker) ➔ although increased somatic and dendritic accumulation of BDNF |
|
| Glutamate (15 min) | Reduced by: TTX | ||||
| Leschik et al. 2013 | Embryonic stem cell derived neurons |
Live cell imaging BDNF-GFP |
Elevated extracellular K+ |
Similar release properties of BDNF–GFP in ESC-derived neurons and transiently transfected hippocampal neurons | |
| Petoukhov et al. 2013 | Rat; hippocampal cultures | Live cell imaging | 4-AP |
BDNF is localized in progranulin positive vesicles in dendrites and axons Release reduced by: Ca-free solution; CdCl2 |
|
| Kolarow et al. 2014 | Rat; hippocampal cultures | Live cell imaging | potassium |
Reduced by SNP (NO-donor) Not affected by: L-NMMA (NOS-inhibitor) |
|
| Lu et al. 2014 | Rat; hippocampal slices; embryonic hippocampal cultures | TrkB-IgG; live cell imaging (BDNF-GFP) | Timing: bAPs + iontophoretic glutamate pulses |
No release by bAPs or iontophoretic glutamate alone Reduced by: APV |
|
| Edelmann et al. 2015 | Organotypic slice; hippocampal slices | Live cell imaging | 20 Hz + 8-Br-cAMP | ||
| Elevated K+ | |||||
| Shimojo et al. 2015 | Cortical cultures | Live cell imaging; BDNF-pHluorin | Elevated extracellular K+ |
Axonal and dendritic BDNF-containing vesicles are localized to Syb2, SNAP25 and SNAP47 Full vesicle collapse is reduced in SNAP 47 kd cultures Partial vesicle collapse is reduced in axons of SNAP 47 kd cultures |
|
| Wong et al. 2015 | Neuronal culture | BDNF-quantum dots | TBS | Axonal and dendritic localization of endocytosed BDNF-QD reduced by Cd2+; CNQX; APV; CNQX + APV; syt-6 siRNA; Complexin siRNA | |
| BDNF-GFP | TBS |
Increased after syt4-siRNA Not affected by syt6-siRNA |
|||
| Baj et al. 2016 | Rat; hippocampal neurons | ELISA | Potassium (3h) |
Translation-dependent BDNF increase Release reduced by: cycloheximide |
|
| Eckenstaler et al. 2016 | Rat; hippocampal cultures; P0-P3, DIV 11-13; BDNF-GFP | Live cell imaging BDNF-GFP | Elevated extracellular K+ |
CAPS1 siRNA: Increase of intragranular pH from 5.8 to 6.7 Reduced incidence of fusion events from 20 % to 10 % Decreased amount of released BDNF per vesicle Not affected: cytosolic pH |
|
|
Inhibition of V-ATPase: reduced incidence for fusion events and reduced BDNF content release | |||||
| Harward et al. 2016 | Cortical cultures; organotyipic slice | TrkB-IgG; live cell imaging; postsynaptic BDNF deletion | Glutamate uncaging |
Reduced by APV; APV + NBQX; CN21 (inhibitor of CAMKII) Not affected by: NBQX |
|
| Henry et al. 2018 | Rat; hippocampal cultures | BDNF knockdown | Inhibition of AMPAR (3h) | mTor dependent translation of postsynaptic BDNF release mediates presynaptic increase in mEPSC frequency | |
| Lin et al. 2018 | Hippocampal slice | Deletion of BDNF in CA1 region | 100 Hz-HFS | “Postsynaptic release”: LTP maintenance + increase in presynaptic release probability | |
| Brigadski et al. 2019 | Rat; hippocampal cultures | Live cell imaging | Elevated extracellular K+ | comparable release kinetics in response to high potassium depolarization vs. electrophysiological stimulation | |
| Depolarization | |||||
| bAP | |||||
| Leschik et al. 2019 | BDNF-GFP-knockin mouse, hippocampal cultures, expression regulated by endogenous BDNF promotor | Live cell imaging BDNF-GFP | Elevated extracellular K+ |
Identical release properties of endogenous BDNF–GFP and overexpressed BDNF-GFP 20 % fusion events 60 % content release Max. of fusion events within 20 s of stimulation; fusion events at 100 s still prominent |
|
| Persoon et al. 2019 | Neuronal cultures | Live cell imaging | Elevated K+ | Rab3a, RIM1/2, Munc13 localized to BDNF-containing granules | |
| BDNF release from axons | |||||
| Kohara et al. 2001 | Mouse, cortical cultures | GFP-IR | Analysis of somatic BDNF-GFP Endocytosis |
Increased by: picrotoxin for 48 hours Reduced by: TTX (48 h); TrkB IgG (48 h) |
|
| Zakharenko et al. 2003 | Hippocampal slice | Deletion of BDNF | 200Hz-HFS | ||
| Dean et al. 2009 |
Rat: E18-20 Mice: P1-3 |
Live cell imaging; BDNF-pHluorin | Potassium |
Increased after syt-IV knockout; Reduced after syt-IV overexpression Regulation of mEPSC frequency |
|
| Matsuda et al. 2009 | Rat, E18-20; neuronal cultures | Live cell imaging; BDNF-pHluorin | TBS | transient fusion pore opening | |
| 50Hz (3min) or TBS (36 trains) | Induction of net BDNF release | ||||
| Field stimulation |
Analysis of transient fusion events Reduced by: Bafilomycin; Dynasore; Cd2+ Not affected by K252a, TrkB-Fc; CNQX, APV; CNQX; APV; nimodipine |
||||
| Loose patch stimulation |
Analysis of transient fusion events Not affected by: nimodipine; CNQX, APV; CNQX; APV |
||||
| Shinoda et al. 2011 | Mouse; hippocampal culture | Live cell imaging; BDNF-pHluorin | Potassium |
Increased after: CAPS2 transfection Reduced after : CAPS2 knockout |
|
| Sadakata et al. 2012 | Mouse, hippocampal granule cell cultur | GFP-IR | Potassium | Reduced after : CAPS2 with deletion of exon3 | |
| Petoukhov et al. 2013 | Rat; hippocampal cultures | Live cell imaging | 4-AP |
BDNF is localized to progranulin positive granules in dendrites and axons Release reduced by: Ca-free solution; CdCl |
|
| Shimojo et al. 2015 | Cortical culture; P1 | Live cell imaging; BDNF-pHluorin | Potassium |
Axonal and dendritic BDNF-containing vesicles are localized to Syb2, SNAP25 and SNAP47 Full vesicle collapse is reduced in SNAP 47 kd cultures partial vesicle collapse is reduced in axons of SNAP 47 kd cultures |
|
| Lin et al. 2018 | Hippocampal slice; | Deletion of BDNF in CA3 | 100Hz-HFS | “presynaptic release”: LTP-induction + LTP maintenance + increase in presynaptic release probability | |
| Park 2018 | Mouse; corticostriatal slice | BDNF-pHluorin | TBS |
reduced by APV (presynaptic NMDAR); CPA (depletion of internal Calcium store); requires GluN1 subunit not affected by dopamine |
|
| HFS without Mg2+ in extracellular solution | reduced by APV | ||||
| Persoon et al. 2019 | Neuronal culture | Live cell imaging | Potassium | Rab3a, RIM1/2, Munc13 localized to BDNF-containing granules | |
List of references for somatic and dendritic release of BDNF. 4-AP 4, amino-pyridine; A2AR, adenosine A2A receptor; Aβ, amyloid-β; ACPD, 1-amino-1,3 dicarboxy cyclopentane; ATP, adenosine triphosphate; Br-cAMP, brom-adenosine 3′5′-cyclic monophosphate; CAMKII, Ca2+-calmodulin-dependent protein kinase II; CAPS, calcium-activated protein for secretion; CNQX, 6-cyano-7-nitroquinoxaline-2,3-dione; D-APV, D(−)-2- amino-5-phosphonovalerate; DIV, days in vitro; E, embryonic day; ELISA, enzyme-linked immunosorbent assay; EP2, prostaglandin E receptor subtype2; GABABR, g aminobutyric acid; HFS, high-frequency stimulation; ITI, intertrain-interval; IP3, inositol triphosphate; IR, immunreactivity; LPS, lipopolysaccharide; NaV, voltage-gated sodium channel; NBQX, 2,3-dihydroxy-6- nitro-7-sulfamoyl-benzo(F)quinoxaline; NMDAR, N-methyl d-aspartate receptor; P, postnatal day; P2XR, P2X purino receptor; p38MAPK, p38 mitogen-activated protein kinase; PAR1-AP, protease-activated receptor activating peptide, PCP, phenylcyclidine; PKA, protein kinase A; PKC, protein Kinase C.; PLC, phospholipase C; SpH, superecliptic pHluorin; syt-IV, synaptotagmin-IV; TBS, theta-burst stimulation; TTX, tetrodotoxin; VGCC, voltage-gated calcium channels; TRPC, transient receptor potential channel