Hypercapnia-induced activation of brainstem GABAergic neurons during early development

During early development, GABAergic mechanisms contribute to the regulation of respiratory timing in response to CO 2. In 5–7 day old piglets, a double labeling technique was used to determine whether GABA-containing neurons are activated by normoxic hypercapnia (10% CO 2, 21% O 2, and 69% N 2). The...

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Bibliographic Details
Published in:Respiratory physiology & neurobiology 2003-06, Vol.136 (1), p.25-37
Main Authors: Zhang, L., Wilson, C.G., Liu, S., Haxhiu, M.A., Martin, R.J.
Format: Article
Language:English
Subjects:
Analysis of Variance
Animals
Animals, Newborn
Biological and medical sciences
Brain Stem - growth & development
Brain Stem - pathology
c-Fos
Carbon dioxide
Carbon Dioxide - pharmacology
Cell Count
Control of breathing
Development
Fundamental and applied biological sciences. Psychology
GABA
GABAergic mechanisms
gamma-Aminobutyric Acid - metabolism
Gene
Hypercapnia - physiopathology
Immunohistochemistry - methods
Mammals
Neurons - metabolism
Parvalbumins - metabolism
Pattern of breathing
piglet
Proto-Oncogene Proteins c-fos - metabolism
respiratory timing
Swine
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Summary:During early development, GABAergic mechanisms contribute to the regulation of respiratory timing in response to CO 2. In 5–7 day old piglets, a double labeling technique was used to determine whether GABA-containing neurons are activated by normoxic hypercapnia (10% CO 2, 21% O 2, and 69% N 2). The c-Fos gene encoded protein (c-Fos) was employed to localize CO 2 activated cells within the piglet medulla oblongata. Parvalbumin was used as a marker for GABAergic neurons. In animals breathing room air, only scant c-Fos-like immunoreactive neurons were observed. A marked increase in c-Fos positive cells was induced after a 60 min exposure to hypercapnia. Colocalization studies revealed that hypercapnia significantly increased c-Fos expression in GABA-containing neurons in the medulla oblongata, especially in the ventral aspect of the medulla, within the Bötzinger region, the gigantocellular reticular nucleus, and the caudal raphe nuclei. Only a few double-labeled cells were observed within the nucleus tractus solitarius. Therefore, brainstem GABAergic neurons are part of the neural networks that respond to CO 2 and may contribute to respiratory frequency responses to hypercapnia during early development.
ISSN:1569-9048
1878-1519
DOI:10.1016/S1569-9048(03)00041-7