PMID- 10995552
OWN - NLM
STAT- MEDLINE
DCOM- 20001121
LR  - 20161124
IS  - 1044-7431 (Print)
IS  - 1044-7431 (Linking)
VI  - 16
IP  - 3
DP  - 2000 Sep
TI  - Attenuation of a caspase-3 dependent cell death in NT4- and p75-deficient 
      embryonic sensory neurons.
PG  - 258-68
AB  - Neuronal survival during the developmental period of naturally occurring cell 
      death is mediated through a successful competition for limiting concentrations of 
      neurotrophic factors, and the deprived neurons will die. New results show that 
      induced death through the p75 neurotrophin receptor (p75(NTR)), a member of the 
      p55TNF/Fas family of cell death receptors, may also influence survival during 
      development. We find that eliminating p75(NTR) or neurotrophin 4 (NT4) in mice 
      leads to a marked attenuation of apoptosis during the programmed cell death 
      period of the trigeminal ganglion neurons, suggesting that NT4 can induce the 
      death of these neurons through the p75(NTR). These in vivo findings were 
      reproduced in primary cell cultures, where NT4 was found to induce death in a 
      p75(NTR)-dependent pathway. Analysis of p75 deficient and wild-type cells 
      revealed two separate cell death pathways, a p75(NTR)- and caspase-3-independent 
      pathway activated by trophic factor deprivation, and a p75(NTR)- and 
      caspase-3-dependent pathway initiated by NT4. Crossing in the NT4 null alleles in 
      brain-derived neurotrophic factor (BDNF) null mutant mice led to a rescue of a 
      large proportion of BDNF-dependent neurons from excessive cell death, indicating 
      that trophic factor deprivation is not sufficient for the death of many neurons 
      and that additional death inducing signals might be required. Our results suggest 
      that NT4 competitively signals survival and death of sensory neurons through trkB 
      and p75(NTR), respectively.
CI  - Copyright 2000 Academic Press.
FAU - Agerman, K
AU  - Agerman K
AD  - Department of Medical Biochemistry and Biophysics, Laboratory of Molecular 
      Neurobiology, Berzeliusv. 3, Karolinska Institutet, Stockholm, 171 77, Sweden.
FAU - Baudet, C
AU  - Baudet C
FAU - Fundin, B
AU  - Fundin B
FAU - Willson, C
AU  - Willson C
FAU - Ernfors, P
AU  - Ernfors P
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Mol Cell Neurosci
JT  - Molecular and cellular neurosciences
JID - 9100095
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Nerve Growth Factors)
RN  - 0 (Receptor, Nerve Growth Factor)
RN  - EC 3.4.22.- (Casp3 protein, mouse)
RN  - EC 3.4.22.- (Caspase 3)
RN  - EC 3.4.22.- (Caspases)
RN  - P658DCA9XD (neurotrophin 4)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/deficiency/genetics
MH  - Caspase 3
MH  - Caspases/*physiology
MH  - Cell Death/physiology
MH  - Cells, Cultured
MH  - Mice/embryology
MH  - Mice, Mutant Strains/genetics
MH  - Nerve Growth Factors/*deficiency/genetics
MH  - Neurons, Afferent/*physiology
MH  - Receptor, Nerve Growth Factor/*deficiency/genetics
EDAT- 2000/09/21 11:00
MHDA- 2001/02/28 10:01
CRDT- 2000/09/21 11:00
PHST- 2000/09/21 11:00 [pubmed]
PHST- 2001/02/28 10:01 [medline]
PHST- 2000/09/21 11:00 [entrez]
AID - S1044-7431(00)90875-3 [pii]
AID - 10.1006/mcne.2000.0875 [doi]
PST - ppublish
SO  - Mol Cell Neurosci. 2000 Sep;16(3):258-68. doi: 10.1006/mcne.2000.0875.