PMID- 11331378
OWN - NLM
STAT- MEDLINE
DCOM- 20010621
LR  - 20240109
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Print)
IS  - 0270-6474 (Linking)
VI  - 21
IP  - 10
DP  - 2001 May 15
TI  - Endogenous brain-derived neurotrophic factor and neurotrophin-3 antagonistically 
      regulate survival of axotomized corticospinal neurons in vivo.
PG  - 3492-502
AB  - Neuronal growth factors regulate the survival of neurons by their survival and 
      death-promoting activity on distinct populations of neurons. The neurotrophins 
      nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and 
      neurotrophin-3 (NT-3) promote neuronal survival via tyrosine kinase (Trk) 
      receptors, whereas NGF and BDNF can also induce apoptosis in developing neurons 
      through p75(NTR) receptors in the absence of their respective Trk receptors. 
      Using mutant mice and inactivation of neurotrophins and their receptors with 
      antibodies in rats, we show that endogenous NT-3 induces death of adult 
      BDNF-dependent, axotomized corticospinal neurons (CSNs). When NT-3 is 
      neutralized, the neurons survive even without BDNF, suggesting complete 
      antagonism. Whereas virtually all unlesioned and axotomized CSNs express both 
      trkB and trkC mRNA, p75 is barely detectable in unlesioned CSNs but strongly 
      upregulated in axotomized CSNs by day 3 after lesion, the time point when cell 
      death occurs. Blocking either cortical TrkC or p75(NTR) receptors alone prevents 
      death, indicating that the opposing actions of NT-3 and BDNF require their 
      respective Trk receptors, but induction of death depends on p75(NTR) cosignaling. 
      The results show that neuronal survival can be regulated antagonistically by 
      neurotrophins and that neurotrophins can induce neuronal death in the adult 
      mammalian CNS. We further present evidence that signaling of tyrosine kinase 
      receptors of the trk family can be crucially involved in the promotion of 
      neuronal death in vivo.
FAU - Giehl, K M
AU  - Giehl KM
AD  - University of Saarland, Department of Anatomy, 66421 Homburg/Saar, Germany. 
      k.giehl@rz.uni-sb.de
FAU - Rohrig, S
AU  - Rohrig S
FAU - Bonatz, H
AU  - Bonatz H
FAU - Gutjahr, M
AU  - Gutjahr M
FAU - Leiner, B
AU  - Leiner B
FAU - Bartke, I
AU  - Bartke I
FAU - Yan, Q
AU  - Yan Q
FAU - Reichardt, L F
AU  - Reichardt LF
FAU - Backus, C
AU  - Backus C
FAU - Welcher, A A
AU  - Welcher AA
FAU - Dethleffsen, K
AU  - Dethleffsen K
FAU - Mestres, P
AU  - Mestres P
FAU - Meyer, M
AU  - Meyer M
LA  - eng
GR  - P01 NS016033/NS/NINDS NIH HHS/United States
GR  - P01 NS016033-180014/NS/NINDS NIH HHS/United States
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 (Antibodies, Blocking)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Neurotrophin 3)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptor, Nerve Growth Factor)
RN  - 0 (Receptors, Nerve Growth Factor)
RN  - EC 2.7.10.1 (Receptor, trkC)
SB  - IM
MH  - Animals
MH  - Antibodies, Blocking/administration & dosage
MH  - Axotomy
MH  - Brain-Derived Neurotrophic Factor/antagonists & 
      inhibitors/pharmacology/*physiology
MH  - Cell Death/physiology
MH  - Cell Survival/drug effects/physiology
MH  - Drug Antagonism
MH  - Female
MH  - Gene Expression/drug effects
MH  - Heterozygote
MH  - Immunohistochemistry
MH  - Infusions, Parenteral
MH  - Male
MH  - Mice
MH  - Mice, Mutant Strains
MH  - Neurons/drug effects/*metabolism
MH  - Neurotrophin 3/antagonists & inhibitors/pharmacology/*physiology
MH  - Pyramidal Tracts/anatomy & histology/drug effects/*metabolism
MH  - RNA, Messenger/analysis/biosynthesis
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptor, Nerve Growth Factor
MH  - Receptor, trkC/antagonists & inhibitors/genetics/metabolism
MH  - Receptors, Nerve Growth Factor/antagonists & inhibitors/genetics/metabolism
MH  - Signal Transduction/drug effects
PMC - PMC2710112
MID - NIHMS112793
EDAT- 2001/05/23 10:00
MHDA- 2001/06/22 10:01
PMCR- 2001/11/15
CRDT- 2001/05/23 10:00
PHST- 2001/05/23 10:00 [pubmed]
PHST- 2001/06/22 10:01 [medline]
PHST- 2001/05/23 10:00 [entrez]
PHST- 2001/11/15 00:00 [pmc-release]
AID - 21/10/3492 [pii]
AID - 5214 [pii]
AID - 10.1523/JNEUROSCI.21-10-03492.2001 [doi]
PST - ppublish
SO  - J Neurosci. 2001 May 15;21(10):3492-502. doi: 10.1523/JNEUROSCI.21-10-03492.2001.