Developmental changes of serotonin 4(a) receptor expression in the rat pre-Bötzinger complex.
Serotonin receptors (5-HTRs) are known to be involved in the regulation of breathing behavior and to mediate neurotrophic actions that exert a significant function in network formation during development. We studied neuronal 5-HT(4(a))R-immunoreactivity (-IR) at developmental ages from E14 to P10. Within the pre-Bötzinger complex (pre-BötC), a part of the respiratory network important for rhythmogenesis, 5-HT(4(a))R-IR was most extensive in rats at an age of E18. The 5-HT(4(a))-IR was found predominantly in the neuropil, whereas somatic staining was sporadic at late embryonic (E18-E20) stages. At birth, we observed a dramatic change to a predominantly somatic staining, and neuropil staining was greatly reduced and disappeared at an age of P4. In all developmental stages, 5-HT(4(a)) and mu-opioid receptors were strongly coexpressed in neurons of the pre-BötC, whereas 5-HT(4(a))R expression was absent in neurons within the dorsal horn. Nestin, a marker for CNS progenitor cells, was used to obtain information about the degree of pre-BötC differentiation. Nestin-positive cells did not appear within the pre-BötC before age E20. At E16, nestin-expressing cells were absent in the nucleus ambiguus (NA) and its ventral periphery. The number of nestin-positive cells increased after birth within and outside the pre-BötC, the majority of cells being glial. Coexpression of nestin and 5-HT(4(a))R was localized predominantly within the NA and appeared only sporadically within the pre-BötC. We conclude that 5-HT(4(a))Rs are important not only for neuromodulation of cellular excitability but also for respiratory network formation.
Manzke
Till
T
Department of Neuro- and Sensory Physiology, Georg-August-University of Göttingen, 37073 Göttingen, Germany. tmanzke@gwdg.de
Preusse
Stefan
S
Hülsmann
Swen
S
Richter
Diethelm W
DW
D000818:Animals; D002940:Circadian Rhythm / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007381:Intermediate Filament Proteins / Q000378:metabolism; D008526:Medulla Oblongata / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D064231:Nestin; D009474:Neurons / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017450:Receptors, Opioid, mu / Q000378:metabolism; D044422:Receptors, Serotonin, 5-HT4 / Q000378:metabolism*; D012125:Respiratory Center / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D013234:Stem Cells; D014018:Tissue Distribution
D007381:Intermediate Filament Proteins; D009419:Nerve Tissue Proteins; C577486:Nes protein, rat; D064231:Nestin; D017450:Receptors, Opioid, mu; D044422:Receptors, Serotonin, 5-HT4