scholarly journals Role of brain-derived neurotrophic factor in hyperoxia-induced enhancement of contractility and impairment of relaxation in lung parenchyma

2008 ◽  
Vol 295 (2) ◽  
pp. L348-L355 ◽  
Author(s):  
Ramadan B. Sopi ◽  
Richard J. Martin ◽  
Musa A. Haxhiu ◽  
Ismail A. Dreshaj ◽  
Qin Yao ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Tyrosine Kinase ◽  
Airway Smooth Muscle ◽  
Neurotrophic Factor ◽  
Critical Role ◽  
Lung Parenchyma ◽  
Brain Derived Neurotrophic Factor ◽  
Airway Hyperreactivity ◽  
Rat Pups

Prolonged hyperoxic exposure contributes to neonatal lung injury, and airway hyperreactivity is characterized by enhanced contraction and impaired relaxation of airway smooth muscle. Our previous data demonstrate that hyperoxia in rat pups upregulates expression of brain-derived neurotrophic factor (BDNF) mRNA and protein, disrupts NO-cGMP signaling, and impairs cAMP production in airway smooth muscle. We hypothesized that BDNF-tyrosine kinase B (TrkB) signaling plays a functional role in airway hyperreactivity via upregulation of cholinergic mechanisms in hyperoxia-exposed lungs. Five-day-old rat pups were exposed to ≥95% oxygen or room air for 7 days and administered daily tyrosine kinase inhibitor K-252a (50 μg·kg−1·day−1 ip) to block BDNF-TrkB signaling or vehicle. Lungs were removed for HPLC measurement of ACh or for in vitro force measurement of lung parenchymal strips. ACh content doubled in hyperoxic compared with room air-exposed lungs. K-252a treatment of hyperoxic pups restored ACh content to room air levels. Hyperoxia increased contraction and impaired relaxation of lung strips in response to incremental electrical field stimulation. K-252a administration to hyperoxic pups reversed this increase in contraction and decrease in relaxation. K-252a or TrkB-Fc was used to block the effect of exogenous BDNF in vitro. Both K-252a and TrkB-Fc blocked the effects of exogenous BDNF. Hyperoxia decreased cAMP and cGMP levels in lung strips, and blockade of BDNF-TrkB signaling restored cAMP but not cGMP to control levels. Therefore, hyperoxia-induced increase in activity of BDNF-TrkB receptor signaling appears to play a critical role in enhancing cholinergically mediated contractile responses of lung parenchyma.

Hyperoxia enhances brain-derived neurotrophic factor and tyrosine kinase B receptor expression in peribronchial smooth muscle of neonatal rats

2005 ◽  
Vol 289 (2) ◽  
pp. L307-L314 ◽  
Author(s):  
Qin Yao ◽  
Musa A. Haxhiu ◽  
Syed I. Zaidi ◽  
Shijian Liu ◽  
Anjum Jafri ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Neurotrophic Factor ◽  
Brain Derived Neurotrophic Factor ◽  
Airway Hyperreactivity ◽  
Receptor Expression ◽  
Postnatal Life ◽  
Bdnf Mrna ◽  
Protein Levels ◽  
Rat Pups ◽  
Hyperoxic Exposure

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.

scholarly journals Smooth muscle brain‐derived neurotrophic factor contributes to airway hyperreactivity in a mouse model of allergic asthma

2018 ◽  
Vol 33 (2) ◽  
pp. 3024-3034 ◽  
Author(s):  
Rodney D. Britt ◽  
Michael A. Thompson ◽  
Sarah A. Wicher ◽  
Logan J. Manlove ◽  
Anne Roesler ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Mouse Model ◽  
Allergic Asthma ◽  
Neurotrophic Factor ◽  
Brain Derived Neurotrophic Factor ◽  
Airway Hyperreactivity

scholarly journals TRPC3 regulates release of brain-derived neurotrophic factor from human airway smooth muscle

2013 ◽  
Vol 1833 (12) ◽  
pp. 2953-2960 ◽  
Author(s):  
Pawan K. Vohra ◽  
Michael A. Thompson ◽  
Venkatachalem Sathish ◽  
Alexander Kiel ◽  
Calvin Jerde ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Neurotrophic Factor ◽  
Brain Derived Neurotrophic Factor ◽  
Human Airway Smooth Muscle ◽  
Human Airway

The effects of brain-derived neurotrophic factor and metformin on in vitro developmental competence of bovine oocytes

Zygote ◽  
2009 ◽  
Vol 17 (3) ◽  
pp. 187-193 ◽  
Author(s):  
So Gun Hong ◽  
Goo Jang ◽  
Hyun Ju Oh ◽  
Ok Jae Koo ◽  
Jung Eun Park ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Embryo Development ◽  
Neurotrophic Factor ◽  
Brain Derived Neurotrophic Factor ◽  
Early Embryo ◽  
Developmental Competence ◽  
Blastocyst Development ◽  
Cell Stage ◽  
Significant Difference

SummaryBrain-derived neurotrophic factor (BDNF) signalling via tyrosine kinase B receptors may play an important role in ovarian development and function. It has been reported that metformin elevates the activity of Tyrosine kinase receptors and may amplify BDNF signalling. The objective of this study was to investigate the effect of BDNF during in vitro maturation (IVM) and/or in vitro culture (IVC) (Experiment 1), and to evaluate the collaborative effect of BDNF and metformin treatment on the developmental competence of bovine in vitro fertilized (IVF) embryos (Experiment 2). In Experiment 1, BDNF, which was added to our previously established IVM systems, significantly increased the proportions of MII oocytes at both 10 ng/ml (86.7%) and 100 ng/ml (85.4%) compared with the control (64.0%). However, there was no statistically significant difference in blastocyst development between the control or BDNF-supplemented groups. In Experiment 2, in order to investigate the effect of BDNF (10 ng/ml) and/or metformin (10−5 M) per se, TCM-199 without serum and hormones was used as the control IVM medium. The BDNF (48.3%) and BDNF plus metformin (56.5%) significantly enhanced the proportions of MII oocytes compared with the control (34.4%). Although, BDNF or metformin alone had no effect in embryo development, BDNF plus metformin significantly improved early embryo development to the 8–16-cell stage compared with the control (16.5 vs. 5.5%). In conclusion, the combination of BDNF and metformin may have a collaborative effect during the IVM period. These results could further contribute to the establishment of a more efficient bovine in vitro embryo production system.

scholarly journals Brain-Derived Neurotrophic Factor Enhances Calcium Regulatory Mechanisms in Human Airway Smooth Muscle

PLoS ONE ◽  
2012 ◽  
Vol 7 (8) ◽  
pp. e44343 ◽  
Author(s):  
Amard J. Abcejo ◽  
Venkatachalem Sathish ◽  
Dan F. Smelter ◽  
Bharathi Aravamudan ◽  
Michael A. Thompson ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Neurotrophic Factor ◽  
Brain Derived Neurotrophic Factor ◽  
Regulatory Mechanisms ◽  
Human Airway Smooth Muscle ◽  
Human Airway

Hyperoxic exposure enhances airway reactivity of newborn guinea pigs

1993 ◽  
Vol 74 (6) ◽  
pp. 2649-2654 ◽  
Author(s):  
C. F. Uyehara ◽  
B. E. Pichoff ◽  
H. H. Sim ◽  
H. S. Uemura ◽  
K. T. Nakamura
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Guinea Pigs ◽  
Airway Hyperreactivity ◽  
Muscle Contractility ◽  
Airway Reactivity ◽  
Smooth Muscle Contractility ◽  
Contractile Responses ◽  
Hyperoxic Exposure

To determine whether altered airway smooth muscle contractility contributes to airway hyperreactivity resulting from hyperoxic exposure, in vitro contractile responses of airways to two physiological constrictors, acetylcholine (10(-9) to 10(-4) M) and histamine (10(-8) to 10(-4) M), were examined. Extrathoracic trachea, intrathoracic trachea, and bronchus from 1- to 2-day-old (newborn) guinea pigs exposed to 85% oxygen for 84 h were compared with tissues obtained from newborns reared in room air. Responses in the presence and absence of aspirin (ASA; 10(-3) M) were compared. Hyperoxic exposure did not affect the histology of the airway epithelia. Contractile responses to acetylcholine and histamine were similar. Without ASA, maximal tensions generated were higher in both extrathoracic and intrathoracic trachea obtained from hyperoxia-exposed neonates than in trachea from newborns reared in room air. ASA caused maximal tensions of trachea from newborns reared in room air to increase but did not affect the already increased contractility of trachea from hyperoxia-exposed animals; the tensions achieved in hyperoxic tissues with and without ASA were similar to the hyperactive responses induced by ASA in tissues from animals reared in room air. Bronchi showed responses similar to those seen in tracheal segments. Thus, despite no apparent histological effect on the airway epithelium, hyperoxic exposure seems to increase airway smooth muscle contractility, is nonspecific for different constricting agents, and shows no regional differences in airway reactivity.

Brain-Derived Neurotrophic Factor in Airway Smooth Muscle

2018 ◽  
pp. 245-261
Author(s):  
Michael Thompson ◽  
Rodney Britt ◽  
Anne Roesler ◽  
Katelyn Cummings ◽  
Christina M. Pabelick ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Neurotrophic Factor ◽  
Brain Derived Neurotrophic Factor
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