Bax-dependent and -independent death of motoneurons after facial nerve injury in adult mice.
Nerve injury-induced neuronal death may occur after accidental trauma or nerve inflammation. Although the response to facial root avulsion has been examined in rodent models, there are conflicting results as to whether motoneuron (MN) death is mediated by apoptosis or necrosis. We examined the response of MNs and proximal nerves after facial nerve avulsion in adult mice. Following facial nerve avulsion in 4-5-week-old mice, we observed a progressive reduction of MNs such that by 4 weeks less than 10% of avulsed MNs remained compared with the control side. The profile of MN degeneration was distinct from axotomy-induced responses. For example, the onset of MN death was more rapid, and the extent of MN loss was greater compared with axotomy. Furthermore, the degeneration of oligodendrocytes and the activation of microglia were increased in the proximal nerve after avulsion. Ultrastructural observations suggested that root avulsion mainly induces non-apoptotic neuronal death, although a small subset of neurons appeared to die via apoptosis. To evaluate the contribution of apoptotic death, we evaluated MN responses in Bax-knockout (KO) mice in which neurons are rescued from apoptotic death. Surprisingly, although the majority of Bax-KO mice exhibited only a moderate MN loss after avulsion, a subset of Bax-KO mice (25%) exhibited extensive MN death and injury-induced changes in the nerve that were indistinguishable from events in wild-type littermates. These results suggest that both Bax-dependent and -independent forms of cell death are evoked by root avulsion, and that programmed cell death may be involved in triggering a robust necrotic response.
Park
Ok-hee
OH
Department of Anatomy, College of Medicine, Korea University, 126-1 Anam-Dong, Sungbuk-Gu, Seoul, Korea 136-705.
Lee
Kea Joo
KJ
Rhyu
Im Joo
IJ
Geum
Dongho
D
Kim
Hyun
H
Buss
Robert
R
Oppenheim
Ronald W
RW
Sun
Woong
W
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001369:Axons / Q000502:physiology; D002452:Cell Count; D016923:Cell Death / Q000502:physiology; D020220:Facial Nerve Injuries / Q000473:pathology*; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017628:Microglia / Q000473:pathology; D008854:Microscopy, Electron; D009046:Motor Neurons / Q000502:physiology* / Q000648:ultrastructure; D009336:Necrosis; D009410:Nerve Degeneration / Q000473:pathology; D009836:Oligodendroglia / Q000473:pathology / Q000502:physiology; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000502:physiology*