Activation of c-Jun and ATF-2 in primate motor cranial nerve nuclei is not associated with apoptosis following axotomy.
Nerve transection induces complex changes in gene regulation and expression that can have profound phenotypic effects on the fate of axotomized neurons. The transcription factors c-Jun and ATF-2 (activating transcription factor-2) are components of a regulatory network that mediates survival, regeneration, and apoptosis following axotomy in rodents. The activation and function of c-Jun and ATF-2 after nerve injury have not been examined in primates. Using a novel model of cranial nerve injury in baboons, we have examined the temporality of c-Jun activation (phosphorylation) in cranial nerve (CN) III and CN VI neurons and ATF-2 activation in CN VI neurons at 2, 4, and 9 days post-injury by immunohistochemistry. Furthermore, we have addressed whether the activation of these factors is associated with apoptosis by the TUNEL assay. We report that activated c-Jun is present in CN III and CN VI neurons ipsilateral to axotomy at 2, 4, and 9 days post-injury, but not in neurons contralateral to injury. Additionally, CN VI neurons ipsilateral to injury at 4 and 9 days contain activated ATF-2. Furthermore, no evidence of TUNEL reactivity was observed in either nucleus, regardless of laterality, at any of the examined time points. These findings suggest that activation of both c-Jun and ATF-2 does not mediate apoptosis in axotomized primate CN III and CN VI neurons at time points up to 9 days. This report serves as a basic inquiry into the neuronal response to cranial nerve injury in primates.
Colby
Geoffrey P
GP
Department of Anatomy and Cell Biology, Columbia University College of Physicians and Surgeons, Black Building Room 1204, 630 West 168th Street, New York, NY 10032, USA.
Coon
Alexander L
AL
Connolly
E Sander
ES
Ambron
Richard T
RT
D000010:Abducens Nerve / Q000166:cytology / Q000378:metabolism; D020222:Abducens Nerve Injury / Q000378:metabolism / Q000503:physiopathology; D051698:Activating Transcription Factor 2; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D019771:Axotomy; D001933:Brain Stem / Q000378:metabolism / Q000473:pathology; D020209:Cranial Nerve Injuries / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D004195:Disease Models, Animal; D018450:Disease Progression; D007839:Functional Laterality / Q000502:physiology; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D009046:Motor Neurons / Q000378:metabolism* / Q000473:pathology; D009802:Oculomotor Nerve / Q000166:cytology / Q000378:metabolism; D061220:Oculomotor Nerve Injuries; D048530:Papio anubis; D010766:Phosphorylation; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D012183:Retrograde Degeneration / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation / Q000502:physiology
D051698:Activating Transcription Factor 2; D017362:Cyclic AMP Response Element-Binding Protein; D016755:Proto-Oncogene Proteins c-jun; D014157:Transcription Factors