Hyperoxia enhances brain-derived neurotrophic factor and tyrosine kinase B receptor expression in peribronchial smooth muscle of neonatal rats.
Airway hyperreactivity is one of the hallmarks of hyperoxic lung injury in early life. As neurotrophins such as brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) are potent mediators of neuronal plasticity, we hypothesized that neurotrophin levels in the pulmonary system may be disturbed by hyperoxic exposure. We therefore evaluated the effects of hyperoxia on the expression of BDNF, NGF, and their corresponding high-affinity receptors, TrkB and TrkA, respectively, in the lung of rat pups. Five-day-old Sprague-Dawley rat pups were randomized to hyperoxic or control groups and then continuously exposed to hyperoxia (>95% oxygen) or normoxia over 7 days. At both mRNA and protein levels, BDNF was detected in lung but not in trachea; its level was substantially enhanced in lungs from the hyperoxia-exposed rat pups. Distribution of BDNF mRNA by in situ hybridization indicates that peribronchial smooth muscle was the major source of increased BDNF production in response to hyperoxic exposure. Interestingly, hyperoxia-induced elevation of BDNF was not accompanied by any changes of NGF levels in lung. Furthermore, hyperoxic exposure increased the expression of TrkB in peribronchial smooth muscle but had no effect on the distribution of the specific NGF receptor TrkA. These findings indicate that hyperoxic stress not only upregulates BDNF at mRNA and protein levels but also enhances TrkB within peribronchial smooth muscle. However, there was no corresponding effect on NGF and TrkA receptors. We speculate that the increased level of BDNF may contribute to hyperoxia-induced airway hyperresponsiveness in early postnatal life.
Yao
Qin
Q
Div. of Neonatology, Rainbow Babies and Children's Hospital, Case Western Reserve Univ., 11100 Euclid Ave., Cleveland, OH 44106, USA.
Haxhiu
Musa A
MA
Zaidi
Syed I
SI
Liu
Shijian
S
Jafri
Anjum
A
Martin
Richard J
RJ
D000818:Animals; D000831:Animals, Newborn; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D001980:Bronchi / Q000166:cytology / Q000378:metabolism*; D018496:Hyperoxia / Q000378:metabolism*; D017403:In Situ Hybridization; D009130:Muscle, Smooth / Q000378:metabolism*; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism; D010100:Oxygen / Q000633:toxicity*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020917:Receptor, trkA / Q000235:genetics / Q000378:metabolism; D020813:Receptor, trkB / Q000235:genetics / Q000378:metabolism*; D014132:Trachea / Q000166:cytology / Q000378:metabolism
D019208:Brain-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D012333:RNA, Messenger; D020917:Receptor, trkA; D020813:Receptor, trkB; D010100:Oxygen