Axotomy-induced apoptotic cell death of neonatal rat facial motoneurons: time course analysis and relation to NADPH-diaphorase activity.
Rapid and massive death of motoneurons occurs following axotomy in neonatal mammals. This likely results from the neurons being deprived of access to target-derived trophic factors, as their death can be prevented by application of a variety of neurotrophic factors to the proximal end of the cut nerve. Since trophic factor-deprived embryonic chick motoneurons undergo apoptosis in vitro, we have investigated whether axotomized neonatal rat facial motoneurons undergo apoptotic cell death in vivo. Following facial nerve transection during the first postnatal day, the dying motoneurons show characteristic morphological changes of apoptosis and undergo DNA fragmentation, as detected by an in situ end labeling technique. An initial sharp burst of DNA fragmentation, between 12 and 24 h postaxotomy, accompanies a steep decline in neuronal numbers, indicating that neuronal cell death rapidly follows endonuclease cleavage of DNA. However, the interval between axotomy and onset of DNA fragmentation varies widely. By 4 days postnatum only 38% of the lesioned motoneurons have survived an initial rapid phase of neuronal loss, whereas 11% survive to 10 days postnatum at least. NADPH-diaphorase/nitric oxide synthase activity has been implicated as having a causal role in the death of lesioned motoneurons. We have found that there is a sustained increase in the intensity of NADPH-diaphorase histochemical staining in axotomized neonatal facial motoneurons, but that this is first detectable well after the onset of DNA fragmentation and cell death. This suggests that nitric oxide, or its metabolites, does not initiate cell death in this model.
Rossiter
J P
JP
Department of Pathology, Queen's University, Kingston, Ontario, Canada.
Riopelle
R J
RJ
Bisby
M A
MA
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D002470:Cell Survival; D005145:Face / Q000294:innervation; D020220:Facial Nerve Injuries; D005260:Female; D008297:Male; D009046:Motor Neurons / Q000166:cytology*; D009252:NADPH Dehydrogenase / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D019001:Nitric Oxide Synthase; D009252:NADPH Dehydrogenase