RESUMO
BACKGROUND: All-trans retinoic acid (atRA) is required for nervous system development, including the developing hindbrain region. Neuron navigator 2 (Nav2) was first identified as an atRA-responsive gene in human neuroblastoma cells (retinoic acid-induced in neuroblastoma 1, Rainb1), and is required for atRA-mediated neurite outgrowth. In this paper, we explore the importance of Nav2 in nervous system development and function in vivo. RESULTS: Nav2 hypomorphic homozygous mutants show decreased survival starting at birth. Nav2 mutant embryos show an overall reduction in nerve fiber density, as well as specific defects in cranial nerves IX (glossopharyngeal) and X (vagus). Nav2 hypomorphic mutant adult mice also display a blunted baroreceptor response compared to wild-type controls. CONCLUSIONS: Nav2 functions in mammalian nervous system development, and is required for normal cranial nerve development and blood pressure regulation in the adult.
Assuntos
Pressão Sanguínea/fisiologia , Nervos Cranianos/crescimento & desenvolvimento , Desenvolvimento Embrionário/genética , Proteínas do Tecido Nervoso/metabolismo , Pressorreceptores/metabolismo , Animais , Pressão Sanguínea/genética , Nervos Cranianos/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Nervo Glossofaríngeo/crescimento & desenvolvimento , Nervo Glossofaríngeo/metabolismo , Homozigoto , Imuno-Histoquímica , Hibridização In Situ , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Mutação , Proteínas do Tecido Nervoso/genética , Neurônios/metabolismo , Neurônios/fisiologia , Pressorreceptores/crescimento & desenvolvimento , Rombencéfalo/crescimento & desenvolvimento , Rombencéfalo/metabolismo , Nervo Vago/crescimento & desenvolvimento , Nervo Vago/metabolismoRESUMO
To investigate postnatal developmental changes in functional characteristics of the afferent pathway of the aortic baroreceptor reflex, the responses of aortic nerve activity (ANA) to blood pressure (BP) changes elicited by phenylephrine and sodium nitroprusside administration were tested in 3-, 8- and 20-week-old male rats under chloralose (60 mg kg(-1) i.p.) and urethane (600 mg kg(-1) i.p.) anaesthesia. The function curve of ANA in response to BP changes showed a sigmoid shape that shifted to the right from 3 to 8 weeks of age. The maximal activity and maximal gain of the aortic nerve, which were calculated by a logistic function analysis, were significantly higher in 20-week-old rats (maximal activity, 532 +/- 47% of baseline; maximal gain, 7.9 +/- 0.8% of baseline mmHg(-1); n = 9) than in 3-week-old rats (maximal ANA, 268 +/- 25% of baseline, P < 0.001; maximal gain, 4.9 +/- 0.5% of baseline mmHg(-1), P < 0.01, n = 9) and 8-week-old rats (maximal ANA, 309 +/- 18% of baseline, P < 0.001; maximal gain, 4.9 +/- 0.3% of baseline mmHg(-1), P < 0.01, n = 11). These results suggest that the operating point of aortic baroreceptor afferents is reset to the higher pressure level during development from 3 to 8 weeks of age and, thereafter, the afferent gain increases from 8 to 20 weeks of age. This functional change may be an important factor to prevent an excess increase of BP, which would result in pathophysiological problems.
