Activation of the c-fos gene in prodynorphin- and proenkephalin-expressing cells of nucleus tractus solitarius after seizures.
We performed studies to determine the anatomical regions and chemical phenotypes of neurons within the rat medulla oblongata activated by pentylenetetrazole-induced seizures. Activated cells were identified by their expression of the c-fos gene, detected by in situ hybridization for c-fos mRNA and immunocytochemistry for Fos protein. Activated cells were located predominantly in nucleus tractus solitarius (NTS), with c-fos mRNA appearing within 20 min after seizures (peak at 1-2 h), followed by Fos immunoreactivity visible at 1 h (peak at 2-4 h). Neither nonspecific noxious stimulation by intraperitoneal injection of saline nor brief exposure to hypoxic or hypercapnic gas mixtures to stimulate chemoreceptors reproduced this pattern of labeling. Prodynorphin or proenkephalin mRNA, detected by in situ hybridization, was colocalized with Fos immunoreactivity in many NTS cells. Thus, seizures activate neuronal pathways in the medulla oblongata which express genes for endogenous opioids. Potential long-term effects of seizures are suggested by the in situ hybridization finding that NTS prodynorphin mRNA increased 24 h after seizures compared to control levels.
Department of Physiology, University of North Carolina, Chapel Hill 27599.
R K
RK
Kanter
J T
JT
Erickson
D E
DE
Millhorn
D000818:Animals; D004745:Enkephalins / Q000032:analysis / Q000096:biosynthesis*; D005786:Gene Expression Regulation; D016762:Genes, fos; D017403:In Situ Hybridization; D008526:Medulla Oblongata / Q000033:anatomy & histology / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000378:metabolism / Q000502:physiology; D010433:Pentylenetetrazole; D011498:Protein Precursors / Q000032:analysis / Q000096:biosynthesis*; D016760:Proto-Oncogene Proteins c-fos / Q000032:analysis / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D017552:Solitary Nucleus / Q000378:metabolism* / Q000503:physiopathology; D013997:Time Factors
D004745:Enkephalins; D011498:Protein Precursors; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; C029992:proenkephalin; C033660:preproenkephalin; D010433:Pentylenetetrazole