PMID- 17522325
OWN - NLM
STAT- MEDLINE
DCOM- 20070622
LR  - 20200225
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Print)
IS  - 0270-6474 (Linking)
VI  - 27
IP  - 21
DP  - 2007 May 23
TI  - Endogenous TrkB ligands suppress functional mechanosensory plasticity in the 
      deafferented spinal cord.
PG  - 5812-22
AB  - Dorsal root injury (DRI) disrupts the flow of sensory information to the spinal 
      cord. Although primary afferents do not regenerate to their original targets, 
      spontaneous recovery can, by unknown mechanisms, occur after DRI. Here, we show 
      that brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3), but not 
      nerve growth factor or neurotrophin-4, are upregulated in the spinal gray matter 
      after DRI. Because endogenous BDNF and NT-3 have well established roles in 
      synaptic and axonal plasticity, we hypothesized that they contributed to 
      spontaneous recovery after DRI. We first developed a model of DRI-induced 
      mechanosensory dysfunction: rat C7/8 DRI produced a deficit in low-threshold 
      cutaneous mechanosensation that spontaneously improved within 10 d but did not 
      recover completely. To determine the effects of endogenous BDNF and NT-3, we 
      administered TrkB-Fc or TrkC-Fc fusion proteins throughout the recovery period. 
      To our surprise, TrkB-Fc stimulated complete recovery of mechanosensation by 6 d 
      after DRI. It also stimulated mechanosensory axon sprouting but prevented 
      deafferentation-induced serotonergic sprouting. TrkC-Fc had no effect on 
      low-threshold mechanosensory behavior or axonal plasticity. There was no 
      mechanosensory improvement with single-bolus TrkB-Fc infusions at 10 d after DRI 
      (despite significantly reducing rhizotomy-induced cold pain), indicating that 
      neuromodulatory effects of BDNF did not underlie mechanosensory recovery. 
      Continuous infusion of the pan-neurotrophin antagonist K252a also stimulated 
      behavioral and anatomical plasticity, indicating that these effects of TrkB-Fc 
      treatment occurred independent of signaling by other neurotrophins. These results 
      illustrate a novel, plasticity-suppressing effect of endogenous TrkB ligands on 
      mechanosensation and mechanosensory primary afferent axons after spinal 
      deafferentation.
FAU - Ramer, Leanne M
AU  - Ramer LM
AD  - International Collaboration on Repair Discoveries, The University of British 
      Columbia, Vancouver, British Columbia, Canada V6T 1Z4.
FAU - McPhail, Lowell T
AU  - McPhail LT
FAU - Borisoff, Jaimie F
AU  - Borisoff JF
FAU - Soril, Lesley J J
AU  - Soril LJ
FAU - Kaan, Timothy K Y
AU  - Kaan TK
FAU - Lee, Jae H T
AU  - Lee JH
FAU - Saunders, James W T
AU  - Saunders JW
FAU - Hwi, Lucy P R
AU  - Hwi LP
FAU - Ramer, Matt S
AU  - Ramer MS
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Neurosci
JT  - The Journal of neuroscience : the official journal of the Society for 
      Neuroscience
JID - 8102140
RN  - 0 (Ligands)
RN  - 0 (Nerve Growth Factors)
RN  - EC 2.7.10.1 (Receptor, trkB)
SB  - IM
MH  - Animals
MH  - Ligands
MH  - Male
MH  - Mechanotransduction, Cellular/drug effects/*physiology
MH  - Nerve Growth Factors/biosynthesis/pharmacology
MH  - Neuronal Plasticity/drug effects/*physiology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptor, trkB/agonists/*physiology
MH  - Spinal Cord Injuries/*metabolism/*physiopathology
PMC - PMC6672770
EDAT- 2007/05/25 09:00
MHDA- 2007/06/23 09:00
PMCR- 2007/11/23
CRDT- 2007/05/25 09:00
PHST- 2007/05/25 09:00 [pubmed]
PHST- 2007/06/23 09:00 [medline]
PHST- 2007/05/25 09:00 [entrez]
PHST- 2007/11/23 00:00 [pmc-release]
AID - 27/21/5812 [pii]
AID - 3226628 [pii]
AID - 10.1523/JNEUROSCI.0491-07.2007 [doi]
PST - ppublish
SO  - J Neurosci. 2007 May 23;27(21):5812-22. doi: 10.1523/JNEUROSCI.0491-07.2007.