Differential neuronal expression of c-fos proto-oncogene following peripheral nerve injury or chemically-induced seizure.
Previous work by others has demonstrated that neocortical injury results in the induction of c-fos protooncogene both at and distal to the site of injury. However, secondary effects of focal brain injury, such as spreading depression and seizure activity, also have been shown to induce the expression of c-fos. Thus, it is unclear whether the stimulus inducing c-fos expression after generalized brain trauma is direct neuronal injury or associated, secondary effects of injury. In this study, we tested the hypothesis that a specific axonal disconnection would induce the expression of c-fos proto-oncogene in the injured neurons. The injury paradigm that was used was peripheral axotomy of rodent facial motoneurons. The right facial nerve was severed distal to the stylomastoid foramen, with the left side serving as an internal control. As positive controls, in a separate group of animals, seizures were invoked using bicuculline administered intraperitoneally. At the end of postoperative survival times ranging from 30 min to 24 hr, the animals were sacrificed. For northern blot analysis using a c-fos cDNA probe, total RNA was isolated from the dissected facial nuclear groups in the injury experiments, or whole brain and neocortex in the seizure experiments. For immunocytochemical analysis using a battery of c-fos antibodies, the animals were perfused with paraformaldehyde and processed for routine light microscope immunocytochemistry. In the bicuculline-injected animals, c-fos mRNA was massively induced in whole brain in a manner proportional to the overall level of gross seizure activity.(ABSTRACT TRUNCATED AT 250 WORDS)
Jones
K J
KJ
Department of Cell Biology and Anatomy, Chicago Medical School, Illinois 60612.
Evinger
C
C
D000818:Animals; D001640:Bicuculline; D015152:Blotting, Northern; D001921:Brain / Q000378:metabolism; D006224:Cricetinae; D004268:DNA-Binding Proteins / Q000378:metabolism; D007150:Immunohistochemistry; D008647:Mesocricetus; D009046:Motor Neurons / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D059348:Peripheral Nerve Injuries; D010525:Peripheral Nerves / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos; D051381:Rats; D012640:Seizures / Q000139:chemically induced / Q000378:metabolism*
D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D001640:Bicuculline