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Nerve growth factor (NGF) induces motoneuron apoptosis in rat embryonic spinal cord in vitro
Author(s) -
Sedel Frédéric,
Béchade Catherine,
Triller Antoine
Publication year - 1999
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1046/j.1460-9568.1999.00814.x
Subject(s) - nerve growth factor , glial cell line derived neurotrophic factor , neurotrophin , neurotrophic factors , low affinity nerve growth factor receptor , embryonic stem cell , biology , neurotrophin 3 , programmed cell death , neuroscience , brain derived neurotrophic factor , apoptosis , microbiology and biotechnology , receptor , endocrinology , medicine , biochemistry , gene
Recent studies have demonstrated that nerve growth factor (NGF) induces apoptosis of several cell types in the central nervous system through its low‐affinity p75 neurotrophin receptor (p75 NTR ). To test the effect of NGF on embryonic motoneuron survival, we developed an organotypic culture system which allowed the in vitro development of intact embryonic rat spinal cords. In our system, neural tubes were taken and cultured at E13, just before the onset of physiological motoneuron death. After 2 days in vitro (DIV), motoneurons underwent apoptosis over a time‐course similar to that in vivo. In this system, the addition of NGF (200 ng/mL) for 2 days enhanced the number of apoptotic motoneurons by 37%. This pro‐apoptotic effect was completely reversed by the blocking anti‐p75 NTR (REX) antibody which inhibits NGF binding to p75 NTR. Other neurotrophins, e.g. brain‐derived neurotrophic factor (BDNF), neurotrophin 3 (NT3) and neurotrophin 4/5 (NT4/5) did not have any effect, while glial cell‐derived neurotrophic factor (GDNF) promoted motoneuron survival. Anti‐BDNF blocking antibodies enhanced motoneuron death indicating that endogenous BDNF promotes motoneuron survival in explants. Our results demonstrate, for the first time, that NGF can induce embryonic motoneuron apoptosis through its receptor p75 NTR.