title: Activation of c-Jun and ATF-2 in primate motor cranial nerve nuclei is not associated with apoptosis following axotomy.
abstract: 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.
authors.affiliation: 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.
authors.forename: Geoffrey P
authors.initials: GP
authors.lastname: Colby
authors.forename: Alexander L
authors.initials: AL
authors.lastname: Coon
authors.forename: E Sander
authors.initials: ES
authors.lastname: Connolly
authors.forename: Richard T
authors.initials: RT
authors.lastname: Ambron
mesh_terms: 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
chemical_list: D051698:Activating Transcription Factor 2; D017362:Cyclic AMP Response Element-Binding Protein; D016755:Proto-Oncogene Proteins c-jun; D014157:Transcription Factors