Postnatal development of brain-derived neurotrophic factor (BDNF) and tyrosine protein kinase B (TrkB) receptor immunoreactivity in multiple brain stem respiratory-related nuclei of the rat

Previously, we found a transient imbalance between suppressed excitation and enhanced inhibition in the respiratory network of the rat around postnatal days (P) 12–13, a critical period when the hypoxic ventilatory response is at its weakest. The mechanism underlying the imbalance is poorly understood. Brain‐derived neurotrophic factor (BDNF) and its tyrosine protein kinase B (TrkB) receptors are known to potentiate glutamatergic and attenuate gamma‐aminobutyric acid (GABA)ergic neurotransmission, and BDNF is essential for respiratory development. We hypothesized that the excitation‐inhibition imbalance during the critical period stemmed from a reduced expression of BDNF and TrkB at that time within respiratory‐related nuclei of the brain stem. An in‐depth, semiquantitative immunohistochemical study was undertaken in seven respiratory‐related brain stem nuclei and one nonrespiratory nucleus in P0–21 rats. The results indicate that the expressions of BDNF and TrkB: 1) in the pre‐Bötzinger complex, nucleus ambiguus, commissural and ventrolateral subnuclei of solitary tract nucleus, and retrotrapezoid nucleus/parafacial respiratory group were significantly reduced at P12, but returned to P11 levels by P14; 2) in the lateral paragigantocellular nucleus and parapyramidal region were increased from P0 to P7, but were strikingly reduced at P10 and plateaued thereafter; and 3) in the nonrespiratory cuneate nucleus showed a gentle plateau throughout the first 3 postnatal weeks, with only a slight decline of BDNF expression after P11. Thus, the significant downregulation of both BDNF and TrkB in respiratory‐related nuclei during the critical period may form the basis of, or at least contribute to, the inhibitory‐excitatory imbalance within the respiratory network during this time. J. Comp. Neurol. 521:109–129, 2013. © 2012 Wiley Periodicals, Inc. A critical period of postnatal respiratory development exists, during which heightened inhibition and suppressed excitation accompany a weak response to hypoxia. We hypothesized that the imbalance stemmed from a reduced expression of brain‐derived neurotrophic factor (BDNF) and its tyrosine protein kinase B (TrkB) receptors, which normally potentiate excitation and attenuate inhibition. Our findings confirmed our hypothesis that the expressions of BDNF and TrkB were significantly reduced in seven respiratory‐related nuclei (but not in a nonrespiratory nucleus) during the critical period.