BDNF is an important regulator of synaptic circuit development, synaptic plasticity and neuroprotection in the brain. Changes in the concentration of BDNF in the human body have been linked to neurodegenerative diseases, neurological diseases, psychological diseases and so on. In order to better understand BDNF concentration changes in vivo, it is important to understand BDNF expression and release. Most studies on BDNF expression and release have been conducted during the preparation and culture of neurons. Therefore, this paper will focus on the expression and release of BDNF in different cells in the brain. In this paper, the synthesis, processing, sorting and induced release of BDNF will be reviewed.
Topics
Review
REFERENCES
1.
Edelmann
E
, Leßmann
V
, Brigadski
T.
Pre- and postsynaptic twists in BDNF secretion and action in synaptic plasticity
. Neuropharmacology [Internet]
. 2014
;76(PART C)
:610
–27
. Available from: 2.
Castrén
E
, Hen
R.
Neuronal plasticity and ant idepressant actions
. Trends Neurosci.
2013
;36
(5
):259
–67
.3.
Holsinger
RMD
, Schnarr
J
, Henry
P
, Castelo
VT
, Fahnestock
M.
Quantitation of BDNF mRNA in human parietal cortex by competitive reverse transcription-polymerase chain reaction: Decreased levels in Alzheimer’s disease
. Mol Brain Res.
2000
;76
(2
):347
–54
.4.
Krishnan
V
, Han
MH
, Graham
DL
, Berton
O
, Renthal
W
, Russo
SJ
, et al Molecular Adaptations Underlying Susceptibility and Resistance to Social Defeat in Brain Reward Regions
. Cell.
2007
;131
(2
):391
–404
.5.
Balietti
M
, Giuli
C
, Conti
F.
Peripheral Blood Brain-Derived Neurotrophic Factor as a Biomarker of Alzheimer’s Disease: Are There Methodological Biases?
Mol Neurobiol.
2018
;55
(8
):6661
–72
.6.
Katoh-Semba
R
, Takeuchi
IK
, Semba
R
, Kato
K.
Distribution of brain-derived neurotrophic factor in rats and its changes with development in the brain
. J Neurochem.
1997
;69
(1
):34
–42
.7.
Nakahashi
T
, Fujimura
H
, Altar
CA
, Li
J
, Kambayashi
JI
, Tandon
NN
, et al Vascular endothelial cells synthesize and secrete brain-derived neurotrophic factor
. FEBS Lett.
2000
;470
(2
):113
–7
.8.
Matthews
VB
, Åström
MB
, Chan
MHS
, Bruce
CR
, Krabbe
KS
, Prelovsek
O
, et al Brain -derived neurotrophic factor is produced by skeletal muscle cells in response to contraction and enhances fat oxidation via activation of AMP-activated protein kinase
. Diabetologia.
2009
;52
(7
):1409
–18
.9.
Barakat-Walter
I.
Brain-derived neurotrophic factor-like immunoreactivity is localized mainly in small sensory neurons of rat dorsal root ganglia
. J Neurosci Methods [Internet].
1996
;68
(2
):281
—288
. Available from: .10.
Yan
Q
, Rosenfeld
RD
, Matheson
CR
, Hawkins
N
, Lopez
OT
, Bennett
L
, et al Expression of brain-derived neurotrophic factor protein in the adult rat central nervous system
. Neuroscience [Internet].
1997
;78
(2
):431
—448
. Available from: 11.
Lessmann
V
, Gottmann
K
, Malcangio
M.
Neurotrophin secretion: Current facts and future prospects
. Prog Neurobiol.
2003
;69
(5
):341
–74
.12.
Zhang
HT
, Li
LY
, Zou
XL
, Song
XB
, Hu
YL
, Feng
ZT
, et al Immunohistochemical distribution of NGF, BDNF, NT-3, and NT-4 in.adult rhesus monkey brains
. J Histochem Cytochem.
2007
;55
(1
):1
–19
.13.
Giannopoulou
I
, Pagida
MA
, Briana
DD
, Panayotacopoulou
MT
. Perinatal hypoxia as a risk factor for psychopathology later in life: the role of dopamine and neurotrophins
. Hormones.
2018
;17
(1
):25
–32
.14.
Pruunsild
P
, Kazantseval
A
, Aid
T
, Palm
K
, Timmusk
T.
Dissecting the human BDNF locus: Bidirectional transcription, complex splicing, and multiple promoters
. Genomics.
2007
;90
(3
):397
–406
.15.
Lessmann
V
, Brigadski
T.
Mechanisms, locations, and kinetics of synaptic BDNF secretion: an update
. Neurosci Res [Internet].
2009
;65
(1
):11
—22
. Available from: 16.
Baj
G
, Carlino
D
, Gardossi
L
, Tongiorgi
E.
Toward a unified biological hypothesis for the BDNF Val66Met-associated memory deficits in humans: A model of impaired dendritic mRNA trafficking
. Front Neurosci.
2013
;7
(OCT):1
–8
.17.
Gidalevitz
T
, Stevens
F
, Argon
Y.
Orchestration of secretory protein folding by ER chaperones
. Biochim Biophys Acta - Mol Cell Res [Internet].
2013
;1833
(11
):2410
–24
. Available from: 18.
Seidah
NG
, Mowla
SJ
, Hamelin
J
, Mamarbachi
AM
, Benjannet
S
, Touré
BB
, et al Mammalian subtilisin/kexin isozyme SKI-1: A widely expressed proprotein convertase with a unique cleavage specificity and cellular localization
. Proc Natl Acad Sci U S A.
1999
;96
(4
):1321
–6
.19.
Mowla
SJ
, Farhadi
HF
, Pareek
S
, Atwal
JK
, Morris
SJ
, Seidah
NG
, et al Biosynthesis and Post-translational Processing of the Precursor to Brain-derived Neurotrophic Factor
. J Biol Chem [Internet].
2001
;276
(16
):12660
–6
. Available from: 20.
Gray
K
, Ellis
V.
Activation of pro-BDNF by the pericellular serine protease plasmin
. FEBS Lett.
2008
;582
(6
):907
–10
.21.
Chen
ZY
, Ieraci
A
, Teng
H
, Dall
H
, Meng
CX
, Herrera
DG
, et al Sortilin controls intracellular sorting of brain-derived neurotrophic factor to the regulated secretory pathway
. J Neurosci.
2005
;25
(26
):6156
–66
.22.
Brigadski
T
, Hartmann
M
, Lessmann
V.
Differential vesicular targeting and time course of synaptic secretion of the mammalian neurotrophins
. J Neurosci.
2005
;25
(33
):7601
–14
.23.
Egan
MF
, Kojima
M
, Callicott
JH
, Goldberg
TE
, Kolachana
BS
, Bertolino
A
, et al The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function
. Cell.
2003
;112
(2
):257
–69
.24.
Jiang
X
, Zhou
J
, Mash
DC
, Marini
AM
, Lipsky
RH
. Human BDNF isoforms are differentially expressed in cocaine addicts and are sorted to the regulated secretory pathway independent of the Met66 substitution
. NeuroMolecular Med.
2009
;11
(1
):1
–12
.25.
Vignoli
B
, Canossa
M.
Glioactive ATP controls BDNF recycling in cortical astrocytes
. Commun Integr Biol [Internet].
2017
;10
(1
):1
–5
. Available from: 26.
Jornot
LH
, Grouzmann
E
, Lacroix
JS
, Rochat
T.
BDNF and DPP-IV in polyps and middle turbinates epithelial cells
. Rhinology.
2007
;45
(2
):129
–33
.27.
López
-Benito
S, Sánchez
-Sánchez
J, Brito
V
, Calvo
L
, Lisa
S
, Torres
-Valle
M, et al Regulation of BDNF release by ARMS/Kidins220 through modulation of synaptotagmin-IV levels
. J Neurosci.
2018
;38
(23
):5415
–28
.28.
Egorov
A V.
, Draguhn
A.
Development of coherent neuronal activity patterns in mammalian cortical networks: Common principles and local hetereogeneity
. Mech Dev [Internet].
2013
;130
(6–8
):412
–23
. Available from: 29.
Brigadski
T
, Leßmann
V.
The physiology of regulated BDNF release. Vol. 382, Cell and Tissue Research. Cell and Tissue Research
; 2020
. 15
–45
p.30.
Baquet
ZC
, Gorski
JA
, Jones
KR
. Early Striatal Dendrite Deficits followed by Neuron Loss with Advanced Age in the Absence of Anterograde Cortical Brain-Derived Neurotrophic Factor
. J Neurosci.
2004
;24
(17
):4250
–8
.31.
Kolarow
R
, Brigadski
T
, Lessmann
V.
Postsynaptic secretion of BDNF and NT-3 from hippocampal neurons depends on calcium-calmodulin kinase II signaling and proceeds via delayed fusion pore opening
. J Neurosci.
2007
;27
(39
):10350
–64
.32.
Kuczewski
N
, Porcher
C
, Ferrand
N
, Fiorentino
H
, Pellegrino
C
, Kolarow
R
, et al Backpropagating action potentials trigger dendritic release of BDNF during spontaneous network activity
. J Neurosci.
2008
;28
(27
):7013
–23
.33.
Matsuda
N
, Lu
H
, Fukata
Y
, Noritake
J
, Gao
H
, Mukherjee
S
, et al Differential activity-dependent secretion of brain-derived neurotrophic factor from axon and dendrite
. J Neurosci.
2009
;29
(45
):14185
–98
.34.
Gubellini
P
, Ben-Ari
Y
, Gaïarsa
JL
. Endogenous neurotrophins are required for the induction of GABAergic long-term potentiation in the neonatal rat hippocampus
. J Neurosci.
2005
;25
(24
):5796
–802
.35.
Fiumelli
H
, Woodin
MA
. Role of activity-dependent regulation of neuronal chloride homeostasis in development
. Curr Opin Neurobiol.
2007
;17
(1
):81
–6
.36.
Kawahara
N
, Croll
SD
, Wiegand
SJ
, Klatzo
I.
Cortical spreading depression induces long-term alterations of BDNF levels in cortex and hippocampus distinct from lesion effects: implications for ischemic tolerance
. Neurosci Res [Internet].
1997
;29
(1
):37
—47
. Available from: 37.
Shen
PP
, Hou
S
, Ma
D
, Zhao
MM
, Zhu
MQ
, Zhang
JD
, et al Cortical spreading depression-induced preconditioning in the brain
. Neural Regen Res.
2016
;11
(11
):1857
–64
.38.
Kojima
M
, Takei
N
, Numakawa
T
, Ishikawa
Y
, Suzuki
S
, Matsumoto
T
, et al Biological characterization and optical imaging of brain-derived neurotrophic factor-green fluorescent protein suggest an activity-dependent local release of brain-derived neurotrophic factor in neurites of cultured hippocampal neurons
. J Neurosci Res.
2001
;64
(1
):1
–10
.39.
Leschik
J
, Eckenstaler
R
, Nieweg
K
, Lichtenecker
P
, Nieweg
K
, Brigadski
T
, et al Embryonic stem cells stably expressing BDNF-GFP exhibit a BDNF-release-dependent enhancement of neuronal differentiation
. J Cell Sci.
2013
;126
(21
):5062
–73
.40.
Leschik
J
, Eckenstaler
R
, Endres
T
, Munsch
T
, Edelmann
E
, Richter
K
, et al Prominent Postsynaptic and Dendritic Exocytosis of Endogenous BDNF Vesicles in BDNF-GFP Knock-in Mice
. Mol Neurobiol.
2019
;56
(10
):6833
–55
.41.
Gottmann
K
, Mittmann
T
, Lessmann
V.
BDNF signaling in the formation, maturation and plasticity of glutamatergic and GABAergic synapses
. Exp Brain Res.
2009
;199
(3–4
):203
–34
.42.
Balkowiec
A
, Katz
DM
. Activity-dependent release of endogenous brain-derived neurotrophic factor from primary sensory neurons detected by ELISA in situ
. J Neurosci.
2000
;20
(19
):7417
–23
.43.
Balkowiec
A
, Katz
DM
. Cellular mechanisms regulating activity-dependent release of native brain-derived neurotrophic factor from hippocampal neurons
. J Neurosci.
2002
;22
(23
):10399
–407
.44.
Meis
S
, Endres
T
, Lessmann
V.
Postsynaptic BDNF signalling regulates long-term potentiation at thalamo-amygdala afferents
. J Physiol.
2012
;590
(1
):193
–208
.45.
Jia
Y
, Gall
CM
, Lynch
G.
Presynaptic BDNF promotes postsynaptic long-term potentiation in the dorsal striatum
. J Neurosci.
2010
;30
(43
):14440
–5
.46.
Lever
IJ
, Bradbury
EJ
, Cunningham JR, Adelson DW, Jones MG, McMahon SB, et al. Brain-derived neurotrophic factor is released in the dorsal horn by distinctive patterns of afferent fiber stimulation
. J Neurosci.
2001
;21
(12
):4469
–77
.47.
Bergami
M
, Santi
S
, Formaggio
E
, Cagnoli
C
, Verderio
C
, Blum
R
, et al Uptake and recycling of pro-BDNF for transmitter-induced secretion by cortical astrocytes
. J Cell Biol.
2008
;183
(2
):213
–21
.48.
Park
H.
Cortical axonal secretion of BDNF in the striatum is disrupted in the mutant-huntingtin knock-in mouse model of huntington’s disease
. Exp Neurobiol.
2018
;27
(3
):217
–25
.49.
Edelmann
E
, Cepeda-Prado
E
, Franck
M
, Lichtenecker
P
, Brigadski
T
, Leßmann
V.
Theta Burs t Firing Recruits BDNF Release and Signaling in Postsynaptic CA1 Neurons in Spike-Timing-Dependent LTP
. Neuron [Internet].
2015
;86
(4
):1041
–54
. Available from: 50.
Li
C
, Dabrowska
J
, Hazra
R
, Rainnie
DG
. Synergistic activation of dopamine D1 and TrKB receptors mediate gain control of synaptic plasticity in the basolateral amygdala
. PLoS One.
2011
;6
(10
).51.
Du JL,
Wei
HP
, Wang
ZR
, Wong
ST
, Poo
MM
. Long-range retrograde spread of LTP and LTD from optic tectum to retina
. Proc Natl Acad Sci U S A.
2009
;106
(45
):18890
–6
.52.
Bi
GQ
, Poo
MM
. Synaptic modifications in cultured hippocampal neurons: Dependence on spike timing, synaptic strength, and postsynaptic cell type
. J Neurosci.
1998
;18
(24
):10464
–72
.53.
Mu
Y
, Poo M
ming
. Spike Timing-Dependent LTP/LTD Mediates Visual Experience-Dependent Plasticity in a Developing Retinotectal System
. Neuron.
2006
;50
(1
):115
–25
.54.
Messaoudi
E
, Ying
SW
, Kanhema
T
, Croll
SD
, Bramham
CR. B
rain-derived neurotrophic factor triggers transcription-dependent, late phase long-term potentiation in vivo
. J Neurosci.
2002
;22
(17
):7453
–61
.55.
Lin
PY
, Kavalali
ET
, Monteggia
LM
. Genetic Dissection of Presynaptic and Postsynaptic BDNF-TrkB Signaling in Synaptic Efficacy of CA3-CA1 Synapses
. Cell Rep [Internet].
2018
;24
(6
):1550
–61
. Available from: 56.
Shelton
DL
, Sutherland
J
, Gripp
J
, Camerato
T
, Armanini
MP
, Phillips
HS
, et al Human trks: Molecular cloning, tissue distribution, and expression of extracellular domain immunoadhesins
. J Neurosci.
1995
;15
(1 II
):477
–91
.57.
Vignoli
B
, Battistini
G
, Melani
R
, Blum
R
, Santi
S
, Berardi
N
, et al Peri-Synaptic Glia Recycles Brain-Derived Neurotrophic Factor for LTP Stabilization and Memory Retention
. Neuron [Internet].
2016
;92
(4
):873
–87
. Available from: 58.
Santi
S
, Cappello
S
, Riccio
M
, Bergami
M
, Aicardi
G
, Schenk
U
, et al Hippocampal neurons recycle BDNF for activity-dependent secretion and LTP maintenance
. EMBO J.
2006
;25
(18
):4372
–80
.59.
Stahlberg
MA
, Kügler
S
, Dean
C.
Visualizing BDNF cell -to-cell transfer reveals astrocytes are the primary recipient of neuronal BDNF
. bioRxiv.
2018
;(September).60.
Rubio
N.
Mouse astrocytes store and deliver brain-derived neurotrophic factor using the non-catalytic gp95trkB receptor
. Eur J Neurosci.
1997
;9
(9
):1847
–53
.61.
Canossa
M
, Griesbeck
O
, Berninger
B
, Campana
G
, Kolbeck
R
, Thoenen
H.
Neurotrophin release by neurotrophins: Implications for activity-dependent neuronal plasticity
. Proc Natl Acad Sci U S A.
1997
;94
(24
):13279
–86
.62.
Saha
RN
, Liu
X
, Pahan
K.
Up-regulation of BDNF in astrocytes by TNF-α: A case for the neuroprotective role of cytokine
. J Neuroimmune Pharmacol.
2006
;1
(3
):212
–22
.63.
Hutchinson
AJ
, Chou
C-L
, Israel
DD
, Xu
W
, Regan
JW
. Activation of EP2 prostanoid receptors in human glial cell lines stimulates the secretion of BDNF
. Neurochem Int [Internet].
2009
;54
(7
):439
—446
. Available from: https://europepmc.org/articles/PMC271700664.
Su
C
, Cunningham
RL
, Rybalchenko
N
, Singh
M.
Progesterone increases the release of brain-derived neurotrophic factor from glia via progesterone receptor membrane component 1 (Pgrmc1)-dependent ERK5 signaling
. Endocrinology.
2012
;153
(9
):4389
–400
.65.
Datta
I
, Ganapathy
K
, Razdan
R
, Bhonde
R.
Location and Number of Astrocytes Determine Dopaminergic Neuron Survival and Function Under 6-OHDA Stress Mediated Through Differential BDNF Release
. Mol Neurobiol.
2018
;55
(7
):5505
–25
.66.
Hou
L
, Liu
Y
, Wang
X
, Ma
H
, He
J
, Zhang
Y
, et al The effects of amyloid-β 42 oligomer on the proliferation and activation of astrocytes in vitro
. Vitr Cell Dev Biol - Anim.
2011
;47
(8
):573
–80
.67.
Seifert
B
, Eckenstaler
R
, Ronicke
R
, Leschik
J
, Lutz
B
, Reymann
K
, et al Amyloid-Beta Induced Changes in Vesicular Transport of BDNF in Hippocampal Neurons
. Neural Plast.
2016
;2016
:19
–21
.68.
Dubbelaar
ML
, Kracht
L
, Eggen
BJL
, Boddeke
EWGM
. The Kaleidoscope of Microglial Phenotypes
. Front Immunol.
2018
;9
(July):1753
.69.
Orecchioni
M
, Ghosheh
Y
, Pramod
AB
, Ley
K.
Macrophage polarization: Different gene signatures in M1(Lps+) vs. Classically and M2(LPS-) vs. Alternatively activated macrophages
. Front Immunol.
2019
;10
(MAY):1
–14
.70.
Werry
EL
, Bright
FM
, Piguet
O
, Ittner
LM
, Halliday
GM
, Hodges
JR
, et al Recent developments in TSPO PET imaging as a biomarker of neuroinflammation in neurodegenerative disorders
. Int J Mol Sci.
2019
;20
(13
):1
–21
.71.
Zhou
D
, Ji
L
, Chen
Y.
TSPO Modulates IL-4-Induced Microglia/Macrophage M2 Polarization via PPAR-γ Pathway
. J Mol Neurosci.
2020
;70
(4
):542
–9
.72.
Merlo
S
, Spampinato
SF
, Beneventano
M
, Sortino
MA
. The contribution of microglia to early synaptic compensatory responses that precede β-amyloid-induced neuronal death
. Sci Rep [Internet].
2018
;8
(1
):1
–11
. Available from: 73.
Nakajima
K
, Tohyama
Y
, Kohsaka
S
, Kurihara
T.
Ceramide activates microglia to enhance the production/secretion of brain-derived neurotrophic factor (BDNF) without induction of deleterious factors in vitro
. J Neurochem.
2002
;80
(4
):697
–705
.74.
Tsuda
M
, Masuda
T
, Tozaki-Saitoh
H
, Inoue K. P2X4 receptors and neuropathic pain
. Front Cell Neurosci.
2013
;7
(OCT):1
–6
.75.
Zhou
LJ
, Peng
J
, Xu
YN
, Zeng
WJ
, Zhang
J
, Wei
X
, et al Microglia Are Indispensable for Synaptic Plasticity in the Spinal Dorsal Horn and Chronic Pain
. Cell Rep.
2019
;27
(13
):3844
-3859
.e6.
This content is only available via PDF.
© 2022 Author(s).
2022
Author(s)
You do not currently have access to this content.
