Inactivation of bcl-2 results in progressive degeneration of motoneurons, sympathetic and sensory neurons during early postnatal development.
Bcl-2 is a major regulator of programmed cell death, a critical process in shaping the developing nervous system. To assess whether Bcl-2 is involved in regulating neuronal survival and in mediating the neuroprotective action of neurotrophic factors, we generated Bcl-2-deficient mice. At birth, the number of facial motoneurons, sensory, and sympathetic neurons was not significantly changed, and axotomy-induced degeneration of facial motoneurons could still be prevented by brain-derived neurotrophic factor (BDNF) or ciliary neurotrophic factor (CNTF). Interestingly, substantial degeneration of motoneurons, sensory, and sympathetic neurons occurred after the physiological cell death period. Accordingly, Bcl-2 is not a permissive factor for the action of neurotrophic factors, and although it does not influence prenatal neuronal survival, it is crucial for the maintenance of specific populations of neurons during the early postnatal period.
Michaelidis
T M
TM
Department of Neurochemistry, Max-Planck-Institute for Psychiatry, Planegg-Martinsried, Federal Republic of Germany.
Sendtner
M
M
Cooper
J D
JD
Airaksinen
M S
MS
Holtmann
B
B
Meyer
M
M
Thoenen
H
H
D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development* / Q000502:physiology; D001369:Axons / Q000502:physiology; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology; D020934:Ciliary Neurotrophic Factor; D003714:Denervation; D005154:Facial Nerve / Q000166:cytology / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009046:Motor Neurons / Q000502:physiology*; D009154:Mutation; D009410:Nerve Degeneration / Q000187:drug effects; D009414:Nerve Growth Factors / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000494:pharmacology; D009474:Neurons / Q000502:physiology*; D009475:Neurons, Afferent / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D013564:Sympathetic Nervous System / Q000166:cytology / Q000502:physiology*
D019208:Brain-Derived Neurotrophic Factor; D020934:Ciliary Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D019253:Proto-Oncogene Proteins c-bcl-2