 |
 Previous Article | Next Article 
The Journal of Neuroscience, June 15, 2001, 21(12):4469-4477
Brain-Derived Neurotrophic Factor Is Released in the Dorsal Horn
by Distinctive Patterns of Afferent Fiber Stimulation
Isobel J.
Lever1,
Elizabeth J.
Bradbury1,
Joanna R.
Cunningham2,
David W.
Adelson3,
Martyn
G.
Jones1,
Stephen B.
McMahon1,
Juan Carlos G.
Marvizón3, and
Marzia
Malcangio1
1 Neuroscience Research Center and
2 Department of Pharmacology, Guy's, King's, and St.
Thomas' School of Biomedical Sciences, King's College London, London
SE1 1UL, United Kingdom, and 3 CURE: Digestive Diseases
Research Center, Neuroenteric Disease Program, Department of Medicine,
University of California, Los Angeles, California 90073
Brain-derived neurotrophic factor (BDNF) is synthesized by small
neuron cell bodies in the dorsal root ganglia (DRG) and is anterogradely transported to primary afferent terminals in the dorsal
horn where it is involved in the modulation of painful stimuli. Here we
show that BDNF is released in the rat isolated dorsal horn after
chemical stimulation by capsaicin or electrical stimulation of dorsal
roots. Capsaicin superfusion (1-100 µM) induced a
dose-dependent release of BDNF, measured using ELISA. The highest dose
of capsaicin also induced a depletion of BDNF protein in the dorsal
horn. BDNF release was also seen after electrical stimulation of the
dorsal roots at C-fiber strength. This release was encoded by specific
patterns of afferent fiber stimulation. Neither continuous
low-frequency (480 pulses, 1 Hz) nor tetanic high-frequency (300 pulses
in 3 trains, 100 Hz) stimulation evoked release of BDNF, although
substance P (SP) release was observed under both of these conditions.
However, BDNF was released after short bursts of high-frequency
stimulation (300 pulses in 75 trains, 100 Hz) along with SP and
glutamate. The NMDA antagonist D-AP-5 inhibited
electrically evoked BDNF release. BDNF release was also measured after
systemic or intrathecal NGF treatment. This upregulated BDNF content in
the DRG and increased the capsaicin-evoked release of BDNF. Similarly,
the amount of BDNF released by burst stimulation was increased after
NGF treatment. This activity-dependent release continued to be encoded
solely by this stimulation pattern. These experiments demonstrate that
BDNF release in the dorsal horn is encoded by specific patterns of
afferent fiber stimulation and is mediated by NMDA receptor activation.
Key words:
neurotrophin release; sensory neurons; capsaicin; burst
stimulation; NMDA receptor; nociception
Copyright © 2001 Society for Neuroscience 0270-6474/01/21124469-09$05.00/0
This article has been cited by other articles:
|
|
|
|
 
A. K. Clark, P. K. Yip, and M. Malcangio
The Liberation of Fractalkine in the Dorsal Horn Requires Microglial Cathepsin S
J. Neurosci.,
May 27, 2009;
29(21):
6945 - 6954.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Sandkuhler
Models and Mechanisms of Hyperalgesia and Allodynia
Physiol Rev,
April 1, 2009;
89(2):
707 - 758.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Trang, S. Beggs, X. Wan, and M. W. Salter
P2X4-Receptor-Mediated Synthesis and Release of Brain-Derived Neurotrophic Factor in Microglia Is Dependent on Calcium and p38-Mitogen-Activated Protein Kinase Activation
J. Neurosci.,
March 18, 2009;
29(11):
3518 - 3528.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. M. Johanek, R. A. Meyer, R. M. Friedman, K. W. Greenquist, B. Shim, J. Borzan, T. Hartke, R. H. LaMotte, and M. Ringkamp
A Role for Polymodal C-Fiber Afferents in Nonhistaminergic Itch
J. Neurosci.,
July 23, 2008;
28(30):
7659 - 7669.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Sha, J. Xu, J. Tang, J. Ding, J. Gong, X. Ge, D. Kong, and X. Gao
Disruption of a novel regulatory locus results in decreased Bdnf expression, obesity, and type 2 diabetes in mice
Physiol Genomics,
October 19, 2007;
31(2):
252 - 263.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Kolarow, T. Brigadski, and V. Lessmann
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.,
September 26, 2007;
27(39):
10350 - 10364.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Kohara, H. Yasuda, Y. Huang, N. Adachi, K. Sohya, and T. Tsumoto
A Local Reduction in Cortical GABAergic Synapses after a Loss of Endogenous Brain-Derived Neurotrophic Factor, as Revealed by Single-Cell Gene Knock-Out Method
J. Neurosci.,
July 4, 2007;
27(27):
7234 - 7244.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Kaku, M. Yokoyama, H. Kobayashi, Y. Matsuoka, T. Sato, S. Mizobuchi, Y. Itano, and K. Morita
Altered Response to Formalin by L5 Spinal Nerve Ligation in Rats: A Behavioral and Molecular Study
Anesth. Analg.,
April 1, 2007;
104(4):
936 - 943.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. Guo, M. T. Robbins, F. Wei, S. Zou, R. Dubner, and K. Ren
Supraspinal Brain-Derived Neurotrophic Factor Signaling: A Novel Mechanism for Descending Pain Facilitation
J. Neurosci.,
January 4, 2006;
26(1):
126 - 137.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Matayoshi, N. Jiang, T. Katafuchi, K. Koga, H. Furue, T. Yasaka, T. Nakatsuka, X.-F. Zhou, Y. Kawasaki, N. Tanaka, et al.
Actions of brain-derived neurotrophic factor on spinal nociceptive transmission during inflammation in the rat
J. Physiol.,
December 1, 2005;
569(2):
685 - 695.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Brigadski, M. Hartmann, and V. Lessmann
Differential Vesicular Targeting and Time Course of Synaptic Secretion of the Mammalian Neurotrophins
J. Neurosci.,
August 17, 2005;
25(33):
7601 - 7614.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Kawasaki, T. Kohno, Z.-Y. Zhuang, G. J. Brenner, H. Wang, C. Van Der Meer, K. Befort, C. J. Woolf, and R.-R. Ji
Ionotropic and Metabotropic Receptors, Protein Kinase A, Protein Kinase C, and Src Contribute to C-Fiber-Induced ERK Activation and cAMP Response Element-Binding Protein Phosphorylation in Dorsal Horn Neurons, Leading to Central Sensitization
J. Neurosci.,
September 22, 2004;
24(38):
8310 - 8321.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Song and J. C. G. Marvizon
Dorsal Horn Neurons Firing at High Frequency, But Not Primary Afferents, Release Opioid Peptides that Produce {micro}-Opioid Receptor Internalization in the Rat Spinal Cord
J. Neurosci.,
October 8, 2003;
23(27):
9171 - 9184.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Kohara, A. Kitamura, N. Adachi, M. Nishida, C. Itami, S. Nakamura, and T. Tsumoto
Inhibitory But Not Excitatory Cortical Neurons Require Presynaptic Brain-Derived Neurotrophic Factor for Dendritic Development, as Revealed by Chimera Cell Culture
J. Neurosci.,
July 9, 2003;
23(14):
6123 - 6131.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Obata, H. Yamanaka, Y. Dai, T. Tachibana, T. Fukuoka, A. Tokunaga, H. Yoshikawa, and K. Noguchi
Differential Activation of Extracellular Signal-Regulated Protein Kinase in Primary Afferent Neurons Regulates Brain-Derived Neurotrophic Factor Expression after Peripheral Inflammation and Nerve Injury
J. Neurosci.,
May 15, 2003;
23(10):
4117 - 4126.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Neal, J. Cunningham, I. Lever, S. Pezet, and M. Malcangio
Mechanism by which Brain-Derived Neurotrophic Factor Increases Dopamine Release from the Rabbit Retina
Invest. Ophthalmol. Vis. Sci.,
February 1, 2003;
44(2):
791 - 798.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. S. Mitchell and S. M. Johnson
Plasticity in Respiratory Motor Control: Invited Review: Neuroplasticity in respiratory motor control
J Appl Physiol,
January 1, 2003;
94(1):
358 - 374.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Balkowiec and D. M. Katz
Cellular Mechanisms Regulating Activity-Dependent Release of Native Brain-Derived Neurotrophic Factor from Hippocampal Neurons
J. Neurosci.,
December 1, 2002;
22(23):
10399 - 10407.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
X. Wang, R. Butowt, M. R. Vasko, and C. S. von Bartheld
Mechanisms of the Release of Anterogradely Transported Neurotrophin-3 from Axon Terminals
J. Neurosci.,
February 1, 2002;
22(3):
931 - 945.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
