Peripheral chemosensitivity and central integration: neuroplasticity of catecholaminergic cells under hypoxia.
The plasticity of catecholaminergic cells within the carotid body, brainstem and sympatho-adrenal system was analyzed in rats subjected to normobaric hypoxia (10% O2) lasting up to 3 weeks. Long-term hypoxia elicited structural, neurochemical and phenotypic changes in carotid body and sympathetic ganglia (SIF cells), and stimulated the norepinephrine turnover in A2 neurons located caudal to the obex, the area where the chemosensory nerve fibers end. Chemodenervation abolished central alterations. Adaptive mechanisms for increasing norepinephrine biosynthesis in hypoxia involved changes in activity of pre-existing tyrosine hydroxylase, the rate-limiting enzyme of catecholamine biosynthesis, and induction of new tyrosine hydroxylase protein. These neurochemical changes occurred after sustained hypoxia only, suggesting that noradrenergic neurons are involved in the central chemoreceptor pathway during sustained hypoxia but are not essential for regulatory responses to acute hypoxia. Acute hypoxia elicited the expression of c-Fos protein in neurons located in nucleus tractus solitarius that were not catecholaminergic. Noradrenaline released under long-term hypoxia could play a neuromodulatory role in ventilatory acclimatization. Cardiovascular responses to hypoxia are mediated by changes in sympatho-adrenal outflow, different according to the target organ. Cardiac sympathetic output and adrenal secretion were stimulated independently of carotid body chemoafferents. Early postnatal hypoxia induced long-term neurochemical changes in carotid body, brainstem and sympathetic efferents that may reveal alterations in development of neurons involved in the chemoreceptor pathway.
Soulier
V
V
UMR 5578 CNRS, Université Claude Bernard, Lyon, France.
Gestreau
C
C
Borghini
N
N
Dalmaz
Y
Y
Cottet-Emard
J M
JM
Pequignot
J M
JM
D000311:Adrenal Glands / Q000201:enzymology / Q000378:metabolism*; D000818:Animals; D001933:Brain Stem / Q000201:enzymology / Q000378:metabolism*; D002344:Carotid Body / Q000201:enzymology / Q000378:metabolism*; D002395:Catecholamines / Q000378:metabolism*; D000860:Hypoxia / Q000201:enzymology / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D009473:Neuronal Plasticity / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013564:Sympathetic Nervous System / Q000201:enzymology / Q000378:metabolism*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D002395:Catecholamines; D014446:Tyrosine 3-Monooxygenase