Specific temporal and spatial distribution of JUN, FOS, and KROX-24 proteins in spinal neurons following noxious transsynaptic stimulation.
We present the first comparative investigation of the basal and transsynaptically induced expression of c-JUN, JUN B, JUN D, c-FOS, FOS B, and KROX-24 proteins in the spinal cord, using immunocytochemistry with specific antibodies. We demonstrate that electrical stimulation of the sciatic nerve at A delta/C-fiber (not A alpha/beta-fiber) intensity strongly induces the expression of these immediate-early gene-encoded proteins. Basal immunoreactivity was found for c-JUN in motoneurons, for JUN D in almost every cell of the gray matter, and for KROX-24 in the superficial dorsal horn. One hour after electrical stimulation of the sciatic nerve at A delta/C-fiber intensity, expression of all proteins except JUN D reached its maximum. Initially immunoreactivity was restricted to the ipsilateral dorsal horn, but after 4 hours appeared contralaterally. Expression of JUN D was increased only after 4 hours. Within the dorsal horn, the expression of c-JUN, JUN B, FOS B, and KROX-24 was mainly restricted to the superficial layers. Immunoreactivity decreased to basal levels between 8 and 16 hours. c-FOS and JUN D were expressed in both the superficial and deep dorsal horn; in the latter, c-FOS and JUN D persisted longer. Induced JUN D was present the longest and was still visible after 32 hours. In motoneurons of the ipsilateral ventral horn, c-JUN, JUN D, and c-FOS appeared after 8 hours. Surgical exposure of the sciatic nerve evoked a strikingly prolonged expression of all proteins compared to that following electrical stimulation of the sciatic nerve. Our results demonstrate that stimulation of nociceptive A delta- and C-fibers induces early and late expression of proteins encoded by immediate-early genes with a specific temporal and spatial distribution of the expression of each protein. Furthermore, the extent of protein expression reflects the intensity of noxious stimulation.
Herdegen
T
T
Physiologisches Institut, Universität Heidelberg, Germany.
Kovary
K
K
Leah
J
J
Bravo
R
R
D000818:Animals; D004268:DNA-Binding Proteins / Q000378:metabolism*; D051766:Early Growth Response Protein 1; D004558:Electric Stimulation; D005786:Gene Expression Regulation; D017874:Immediate-Early Proteins; D007150:Immunohistochemistry; D008297:Male; D009412:Nerve Fibers / Q000502:physiology; D009413:Nerve Fibers, Myelinated / Q000502:physiology; D009474:Neurons / Q000378:metabolism* / Q000502:physiology; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012584:Sciatic Nerve / Q000502:physiology; D013116:Spinal Cord / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D013569:Synapses / Q000502:physiology*; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism*
D004268:DNA-Binding Proteins; D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D017874:Immediate-Early Proteins; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D014157:Transcription Factors