PMID- 11438749
OWN - NLM
STAT- MEDLINE
DCOM- 20010809
LR  - 20240322
IS  - 0027-8424 (Print)
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Linking)
VI  - 98
IP  - 14
DP  - 2001 Jul 3
TI  - BDNF but not NT-4 is required for normal flexion reflex plasticity and function.
PG  - 8107-12
AB  - Neurotrophins can directly modulate the function of diverse types of central 
      nervous system synapses. Brain-derived neurotrophic factor (BDNF) might be 
      released by nociceptors onto spinal neurons and mediate central sensitization 
      associated with chronic pain. We have studied the role of BDNF and neurotrophin-4 
      (NT-4), both ligands of the trkB tyrosine kinase receptor, in synaptic 
      transmission and reflex plasticity in the mouse spinal cord. We used an in vitro 
      spinal cord preparation to measure monosynaptic and polysynaptic reflexes evoked 
      by primary afferents in BDNF- and NT-4-deficient mice. In situ hybridization 
      studies show that both these neurotrophins are synthesized by sensory neurons, 
      and NT-4, but not BDNF, also is expressed by spinal neurons. BDNF null mutants 
      display selective deficits in the ventral root potential (VRP) evoked by 
      stimulating nociceptive primary afferents whereas the non-nociceptive portion of 
      the VRP remained unaltered. In addition, activity-dependent plasticity of the VRP 
      evoked by repetitive (1 Hz) stimulation of nociceptive primary afferents (termed 
      wind-up) was substantially reduced in BDNF-deficient mice. This plasticity also 
      was reduced in a reversible manner by the protein kinase inhibitor K252a. 
      Although the trkB ligand NT-4 is normally present, reflex properties in NT-4 null 
      mutant mice were normal. Pharmacological studies also indicated that spinal 
      N-methyl-d-aspartate receptor function was unaltered in BDNF-deficient mice. 
      Using immunocytochemistry for markers of nociceptive neurons we found no evidence 
      that their number or connectivity was substantially altered in BDNF-deficient 
      mice. Our data therefore are consistent with a direct role for presynaptic BDNF 
      release from sensory neurons in the modulation of pain-related neurotransmission.
FAU - Heppenstall, P A
AU  - Heppenstall PA
AD  - Growth Factors and Regeneration Group, Department of Neuroscience, Max-Delbruck 
      Center for Molecular Medicine, D-13092 Berlin, Germany.
FAU - Lewin, G R
AU  - Lewin GR
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Nerve Growth Factors)
RN  - P658DCA9XD (neurotrophin 4)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*physiology
MH  - Mice
MH  - Mice, Knockout
MH  - Nerve Growth Factors/*physiology
MH  - Nociceptors/physiology
MH  - Reflex/*physiology
MH  - Spinal Cord/*physiology
PMC - PMC35475
EDAT- 2001/07/05 10:00
MHDA- 2001/08/10 10:01
PMCR- 2002/01/03
CRDT- 2001/07/05 10:00
PHST- 2001/07/05 10:00 [pubmed]
PHST- 2001/08/10 10:01 [medline]
PHST- 2001/07/05 10:00 [entrez]
PHST- 2002/01/03 00:00 [pmc-release]
AID - 98/14/8107 [pii]
AID - 141015098 [pii]
AID - 0150 [pii]
AID - 10.1073/pnas.141015098 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2001 Jul 3;98(14):8107-12. doi: 10.1073/pnas.141015098.