Development of pontine noradrenergic A5 neurons requires brain-derived neurotrophic factor.
Pontine noradrenergic A5 neurons play a pivotal role in maturation and regulation of the brainstem respiratory rhythm-generating network. Analysis of newborn brain-derived neurotrophic factor (BDNF)-null mice revealed a marked loss of tyrosine hydroxylase-positive A5 neurons compared to wildtype controls that was rescued by null mutation of the proapoptotic gene Bax. In cultures of the A5 region from E12.5 rat embryos, BDNF significantly increased the number and branching of tyrosine hydroxylase-positive neurons. Immunoneutralization of endogenous glial cell line-derived neurotrophic factor partially inhibited the BDNF-dependent increase in the number of tyrosine hydroxylase-positive cells without affecting neurite number. The A5 nucleus is the first brainstem cell group identified at which BDNF is required in vivo for development of neurons critical for cardiorespiratory control.
Guo
Hong
H
Department of Neurosciences, Case Western Reserve University School of Medicine, 10900 Euclid Avenue, Cleveland, Ohio 44106, USA.
Hellard
David T
DT
Huang
Lennox
L
Katz
David M
DM
D000704:Analysis of Variance; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000494:pharmacology*; D002452:Cell Count; D002478:Cells, Cultured; D004347:Drug Interactions; D004622:Embryo, Mammalian; D005260:Female; D051100:Glial Cell Line-Derived Neurotrophic Factor; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D009414:Nerve Growth Factors / Q000276:immunology; D016501:Neurites / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism*; D011149:Pons / Q000166:cytology* / Q000196:embryology*; D011247:Pregnancy; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D051381:Rats; D014404:Tubulin / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D051028:bcl-2-Associated X Protein
D000906:Antibodies; C494827:Bax protein, mouse; C494828:Bax protein, rat; D019208:Brain-Derived Neurotrophic Factor; C495040:Gdnf protein, mouse; C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D019253:Proto-Oncogene Proteins c-bcl-2; D014404:Tubulin; D051028:bcl-2-Associated X Protein; D014446:Tyrosine 3-Monooxygenase; D009638:Norepinephrine