title: Delayed maturation of catecholamine phenotype in nucleus tractus solitarius of rats with glial angiotensinogen depletion.
abstract: Cerebral catecholamines and angiotensins are both involved in the regulation of cardiovascular function. Recent in vitro studies have suggested that angiotensin II modulates noradrenergic neurotransmission by controlling both the expression and neuritic trafficking of tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine biosynthesis. To assess the potential existence of such mechanisms in vivo, we compared TH phenotype ontogeny in the nucleus tractus solitarius (NTS), which is the first central relay of the baroreflex, between control Sprague-Dawley rats and TGR(ASrAOGEN) rats (TG) with glial specific angiotensinogen (AOGEN) depletion. TG displayed a delayed increase in both TH-mRNA and TH protein levels, which sharply rises in the NTS of control rats within the fourth week. The delayed maturation of TH phenotype also affected the presence of TH protein in the neuropil, not only within the NTS region but also within the ventrolateral medulla. This was evidenced by a large decrease in the density of TH-containing neuronal processes in TG at 4 weeks only, without noticeable modification of the labeling of the neuritic marker MAP2, suggesting that neuritic trafficking of TH protein was transiently altered. These results indicate that glial AOGEN is crucial to coordinate within the fourth week the mechanisms driving the maturation of NTS catecholaminergic neurons and suggest that impairment of the central angiotensinergic system early in development can lead to cardiovascular dysfunction related to altered maturation of catecholaminergic neurons located in both the dorsal and the ventrolateral medulla.
mesh_terms: D000808:Angiotensinogen / Q000235:genetics*; D000818:Animals; D030801:Animals, Genetically Modified; D002395:Catecholamines / Q000096:biosynthesis*; D007700:Kinetics; D009457:Neuroglia / Q000378:metabolism*; D009474:Neurons / Q000737:chemistry / Q000648:ultrastructure; D009638:Norepinephrine / Q000032:analysis; D010641:Phenotype; D016372:RNA, Antisense / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017552:Solitary Nucleus / Q000737:chemistry / Q000254:growth & development* / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis / Q000235:genetics / Q000378:metabolism
chemical_list: D002395:Catecholamines; D016372:RNA, Antisense; D012333:RNA, Messenger; D000808:Angiotensinogen; D014446:Tyrosine 3-Monooxygenase; D009638:Norepinephrine