Table 3.
Neuronal release—exact source of BDNF secretion is unknown, measurement of BDNF by, e.g., ELISA or scavenging of BDNF
| Ref. | Species/type of preparation | Method | Release induction protocol | Pharmacology/molecular mechanism/time course |
|---|---|---|---|---|
| Wetmore et al. 1994 | Rat | Immuno-histochemical staining | Kainat injection | Increase in DNQX dependent transcription of BDNF, irrespective of NMDA activation |
| Goodman et al. 1996 | Rat; E16, hippocampus | Western blot | Potassium | Blocked in At20 cells in calcium-free solution |
| Figurov et al. 1996 | Hippocampal slice | TrkB-IgG | HFS | |
| Kang et al. 1997 | Hippocampal slice | TrkB-IgG | TBS | TrkB-IgG application 0 min and 30 min after LTP induction |
| pairing | ||||
| Canossa et al. 1997 |
Rat; hippocampal culture E17 Hippocampal slice |
ELISA | NT-4 |
Reduced by: K252; BAPTA-AM Not affected by: CNQX; BAPTA |
| NT3 |
Reduced by: K252; BAPTA-AM Not affected by: CNQX; BAPTA |
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| Glutamate |
Reduced to CTRL-level in the presence of CNQX One peak of BDNF release after 20 min Investigated time window: 100 min Not affected by K252a |
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| Chen et al. 1999 | Hippocampal slice | TrkB IgG | TBS | |
| Griesbeck et al. 1999 |
Hippocampal slice Hippocampal cultures from E17 |
ELISA | Potassium (up to 150%) |
Blocked to ctrl-level in the presence of BAPTA-AM (intracellular calcium scavenging) Blocked to ctrl level in the presence of thapsigargin/caffeine Not effected in the presence of BAPTA + calcium free solution |
| Glutamate |
Blocked in the presence of BAPTA-AM (intracellular calcium scavenging) Not effected in the presence of BAPTA + calcium-free solution |
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| Balkowiec and Katz 2000 | Rat; cultures from nodose and petrosal ganglia neurons | ELISA | Potassium (72 h) | Accumulation of BDNF |
| 20 or 50 Hz stimulation |
reduced by TTX No release after 5 Hz or 10 Hz stimulation |
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| 50 Hz TBS | ||||
| Canossa et al. 2001 | Hippocampal slice | ELISA | glutamate | No release after NMDA application |
| AMPA | Reduced by: CNQX; caffeine + thapsigargin | |||
| t-ACPD | Reduced by: AIDA; caffeine + thapsigargin | |||
|
Nnr5 cells Transfected with TrkA |
NGF |
Depedendent on exogenous TrkA expression Blocked by mutatet trkA with mutated PLC-site Reduced by BAPTA/AM; thapsigargin + caffeine |
||
| Patterson et al. 2001 | Mouse; hippocampal slice | TrkB-IgG | TBS | Regulated by cAMP (reduction of forskolin-induced phosphorylation of TrkB in the presence of TrkB-IgG) |
| Balkowiec and Katz 2002 | Rat; hippocampal neurons | ELISA | TBS |
Blocked by TTX; conotoxin; extracellular Ca-free; dantrolene + thapsigargin; Not affected by: CNQX + APV; mGluR inhibitor; nimopidine |
| t-ACPD (activator of mGluR) | Blocked by dantrolene + thapsigargin; | |||
| Canossa et al. 2002 | Rat, hippocampal neurons; E17 | ELISA | Network activity |
Reduction up to 75% in the presence of glutamate receptor antagonists Increase up to 140% 20 min after L-NAME application Reduced after application of SNP (NO-donor); NOR3 (NO-donor); YC1 (agonist of sGC); 8 Br-cGMP Increased by KT5823 (inhibitor of PKG) |
| Gartner and Staiger 2002 | Rat; hippocampal cultures from E19 | ELISA | 50 Hz train |
Reduced by: TTX; Thapsigargin +caffeine; IP3R antagonist Not affected by: NMDAR antagonist; extracellular calcium-free solution |
| Egan et al. 2003 | Rat, hippocampal culture E20 transfected with valBDNF or metBDNF | GFP-ELISA | Potassium | Reduced in neurons transfected with metBDNF-GFP |
| Aicardi et al. 2004 | Hippocampal slice | ELISA | TBS-100 Hz |
Release within 10 min after TBS Reduced BDNF release after LFS (5 Hz or 1 Hz) |
| Ba et al. 2005 | Brain stem spinal cord preparations E16 | ELISA | Basal level |
Reduced by TTX; receptor antagonists Increased by elevated potassium |
| Buldyrev et al. 2006 | Rat; Trigeminal neuronal culture | ELISA | Varying frequency | Reduced by: extracellular calcium-free solution; N-Type VGCC blocker; L-type blocker; P/Q-type VGCC blocker (reduction to 50% after inhibition of one of the receptor) |
| CGRP |
Reduced by: thapsigargin; thapsigarin + dantrolen Not affected by blocker of VGCC (N-, L-, P/Q-type) |
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| Guo et al. 2006 | Rat; brainstem/rostral ventromedial medulla slice | TrkB-phosphorylation; TrkB-IgG | TBS | |
| Santi et al. 2006 | Hippocampal slice incubated with BDNF-YFP | Live cell imaging-release of endo-cytosed BDNF | Basal secretion | Not induced by NMDA application |
| Not induced by NGF | ||||
| Reduced by NO donor NOR3 | ||||
| Potassium | Reduced by k252a | |||
| Glutamate | Recycling reduced by BAPTA-AM | |||
| AMPA | Recycling reduced by CNQX | |||
| t-ACPD | Recycling reduced by AIDA | |||
| caffeine | ||||
| NT-4 | Reduced by K252a | |||
| NT-3 | Reduced by K252a | |||
| 50 Hz | Reduced by TTX | |||
| KT5823 (inhibitor of PKG) | ||||
| Nakajima et al. 2008 | Hippocampal E17 culture |
FRET Cell-based fluorescent indicator for BDNF |
BDNF 3.5 nm | Not affected by TTX; APV + CNQX |
| Glutamate | Reduced by TTX; APV + CNQX | |||
| Tanaka et al. 2008 | Organotypic hippocampal slice | TrkB-IgG | Uncaging glutamate + bAP | Not induced by unpaired stimulus |
| Babu et al. 2009 | Mouse, hippocampal culture P0 | ELISA | Glycine (60 min) | Glycine treatment do not induce NT-3 release |
| Du et al. 2009 | Xenopus retinotectal system with pre and postsynaptic knockdown | Knockdown of site-specific TrkB expression | TBS | |
| Jourdi et al. 2009 | Neuronal cultures | Western blot | CX641 (Ampakine) | Reduced by: CNQX, Ca-free solution; nifedipin; ryanodin |
| Fritsch et al. 2010 | Motor cortex slice | TrkB IgG | Direct current stimulation (DCS)-LTP | |
| Hsieh et al. 2010 | Nodose ganglion neuronal culture | ELISA | 6-Hz stimulation |
Reduced by NOR3 ➔ Rescued by NEM (prevention of s-Nitrosylation) not affected by: YC1 (guanylyl cyclase agonist); KT5823 (PKG antagonist); 8-Br-cGMP |
| Reduced by SNAP (NO donor) ➔ rescued by Tempol (radical scavenger, prevention of S-nitrosylation) | ||||
| Li et al. 2010 |
Hippocampal slice Mossy fiber ➔ CA3 |
TrkB IgG | TBS | MF(IAmpl) reduced in the presence of (glutamate and GABA receptor antagonists) + TTX |
| Li et al. 2011 | Rat; brain slice | TrkB-Fc | TBS | LTP in BLA blocked by TrkB-Fc |
| Porcher et al. 2011 | Cortical neurons | BDNF-IR | Muscimol (10 min) | Reduced by: bicuculine (back to control level) |
| Ctrl | Reduced by: TTX: reduction to 50% | |||
| Meis et al. 2012 | Coronal slices | TrkB-IgG | Pairing protocol: presynaptic 100 Hz + postsynaptic Depolarization |
LTP blocked by APV LTP blocked by Pep1-TGL |
| Chen and Russo-Neustadt 2013 | Rat; E18; hippocampal cultures | ELISA | Norepinephrine | Significant increase after 120 min |
| 5-HT | Significant increase after 10 min | |||
| 5 HT + norepinephrine | Significant increase after 5 min | |||
| Schildt et al. 2013 | Adult mouse; hippocampal slice | TrkB-Fc | 50 Hz stimulation | Reduced MF LTP in the presence of TrkB-Fc |
| Lepack et al. 2014 | Rat; cortical culture; E18 | ELISA | Ketamine | Reduced by verapamil (inhibitor of L-type VGCC) blocked by NBQ (inhibitor of (AMPAR) |
| Briz et al. 2015 | Neuronal cultures | TrkB-Fc; Western blot | Estradiol (1 h) | |
| G1 (1h) |
G1 = G-protein-coupled estrogen receptor 1 agonist (GPER1) Not affected by ERalpha or ERbeta agonists PPT and DPN |
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| Edelmann et al. 2015 | Hippocampal slice | TrkB-IgG | Burst t-LTP | NMDAR-dependent |
| Zhao et al. 2015 | Mouse; somatosensory cortex | TrkB blocking; BDNf rescue | TBS | |
| Hedrick et al. 2016 | Rodent hippocampal slice | TrkB-Fc | Glutamate-uncaging | Heterosynaptic fascilitation of structural LTP |
| Atasoy et al. 2017 | Rat E16 | ELISA | Okadaic acid (24 h) |
No change in BDNF release after Okadaic acid (8 h) Increase in BDNF level |
| Lao-Peregrin et al. 2017 | Mouse, hippocampal slice | ELISA | Caffeine (5 min) | Reduced by TTX; ryanodin |
| Kato et al. 2018 | Rat, primary cortical culture | Western blot; ELISA | GLYX-13 (allosteric modulator of NMDAR) | Reduced by verapamil |
| Lopez-Benito et al. 2018 | DRG and cortical neurons, in vivo, in HD mice | ELISA | Basal levels | Increased by shRNA for ARMS |
| Potassium | Increased by shRNA for ARMS | |||
| NT-3 | Increased by shRNA for ARMS | |||
| NT-4 | Increased by shRNA for ARMS | |||
| Physical activity | In vivo BDNF release in different regions at different time points | |||
| Yu et al. 2018 | Cortical neurons of zQ175 mice (HD model) | BDNF-pHluorin; live cell imaging | 50 Hz | Smaller proportion of BDNF-containing vesicles undergoing full release |
| Zimbone et al. 2018 | Rat; E15 | ELISA | Basal release | Not affected by oligoAbeta |
| Abeta1-42 (100 nM, 24 h) |
Reduced by: selective inhibitor of IGF-IR (picropodophyllin) Not effected by: oligomeric Abeta1-42 Transcription dependent increase in BDNF level; increase in BDNF level to 150% |
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| IGF (5 ng/ml, 24 h) | Transcription dependent increase in BDNF level, increase in BDNF level to 190% | |||
| Fogaça et al. 2019 | Primary cortical culture | ELISA | Methadone (60 min) | |
| Fukumoto et al. 2019 | Cortical culture | ELISA | Hydroxynor-ketamine (60 min) | Reduced by verapamil (inhibitor of L-type VGCC); NBQX (inhibitor of (AMPAR) |
| Lee et al. 2019 | Mouse, cortical neurons, Munc18 ko mice | ELISA | Basal level | Reduced in x/-munc18 ko culture |
| Liu et al. 2019 | Rat | ELISA | Conditioned taste aversion memory extinction (12 h) | |
List of references analyzing molecular mechanisms of BDNF release or the contribution of BDNF during LTP in different neuronal preparations. The exact cellular source of BDNF is unknown since BDNF was either quantified by, e.g., ELISA measurements or the significance of BDNF release was shown by scavenging BDNF from extracellular space. (Abbreviations: please see table legend of Table 1)