Birth-related expression of c-fos, c-jun and substance P mRNAs in the rat brainstem and pia mater: possible relationship to changes in central chemosensitivity.
In situ hybridization was used to characterize respiration-related areas of the brainstem activated around the time of birth as well as their postnatal sensitivity to CO2. Levels of mRNA corresponding to the immediate early genes (IEG), c-fos and c-jun, and of substance P precursor, ppt-A, were determined in rat fetuses (E21) and neonatal pups (1 h, 1 day and 6 days after normal birth) and after exposure to hypercapnia (12% CO2 for 1 h). Transient increases in c-fos mRNA were observed in the central chemoreceptor area of the ventral medullary surface (VMS), in the lateral reticular nucleus (LRN), in the nucleus of the solitary tract (NTS), and in the nucleus raphé pallidus (RPA) 1 h after birth. Increased expression of c-fos mRNA in the VMS could also be evoked by hypercapnia and this response was particularly pronounced 1 day after birth. On the other hand, c-jun mRNA could be detected already at E21 in the hypoglossal nucleus (XII) and LRN and these levels were not significantly altered at 1 h after birth. There was, however, an increase in the expression of c-jun mRNA in the pia mater surrounding the brainstem after birth. At 1 day after birth, c-jun mRNA levels had decreased in the LRN and pia mater, and later on (6 days after birth) in XII. Furthermore, the ppt-A mRNA level in NTS increased immediately after birth and remained high 1 and 6 days later. These results suggest that (a) the central chemoreceptor area of the VMS, as well as the NTS, LRN, RPA and pia mater are activated following birth; (b) the VMS, but not the other structures examined, can be activated immediately after birth by hypercapnia; and (c) increased expression of ppt-A mRNA may be related to the transition of respiratory control at birth.
Wickström
H R
HR
Department of Women and Child Health, Karolinska Institute, S-171 77, Stockholm, Sweden. ronny.wickstrom@kbh.ki.se
Holgert
H
H
Hökfelt
T
T
Lagercrantz
H
H
D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development / Q000378:metabolism; D001921:Brain / Q000196:embryology* / Q000378:metabolism* / Q000502:physiology; D001933:Brain Stem / Q000196:embryology / Q000378:metabolism; D002628:Chemoreceptor Cells / Q000502:physiology; D036861:Delivery, Obstetric; D005314:Embryonic and Fetal Development / Q000502:physiology; D005260:Female; D017781:Genes, Immediate-Early / Q000235:genetics*; D008297:Male; D008526:Medulla Oblongata / Q000378:metabolism; D010841:Pia Mater / Q000196:embryology / Q000378:metabolism; D011498:Protein Precursors / Q000235:genetics; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats / Q000196:embryology; D017207:Rats, Sprague-Dawley; D013373:Substance P / Q000235:genetics*; D015320:Tachykinins / Q000235:genetics
D011498:Protein Precursors; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D015320:Tachykinins; C044206:preprotachykinin; D013373:Substance P