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 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.

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 Brain-derived neurotrophic factor and TrkB levels in mice that lack vesicular zinc: Effects of age and sex

2018 ◽  
Author(s):  
Brendan B. McAllister ◽  
Nicoline Bihelek ◽  
Richelle M. Mychasiuk ◽  
Richard H. Dyck
Keyword(s):  
Mrna Expression ◽  
Knockout Mice ◽  
Neurotrophic Factor ◽  
Brain Derived Neurotrophic Factor ◽  
Receptor Kinase ◽  
Wild Type ◽  
Bdnf Mrna ◽  
Protein Levels ◽  
Intact Brain

ABSTRACTIn certain neurons, zinc ions are stored in synaptic vesicles by zinc transporter 3 (ZnT3). Vesicular zinc can then be released synaptically to modulate myriad targets. In vitro evidence indicates that these targets may include brain-derived neurotrophic factor (BDNF) and its receptor, tropomyosin receptor kinase B (TrkB). But the effects of vesicular zinc on BDNF and TrkB in the intact brain are unclear. Studies of mice that lack ZnT3 – and, as a result, vesicular zinc – have shown abnormalities in BDNF and TrkB levels, but results have been mixed and are therefore difficult to interpret. This might be caused by differences in the age or sex of mice tested. In the present study, we measured BDNF and TrkB levels in the hippocampus and neocortex, comparing wild type and ZnT3 knockout mice of both sexes at two ages (5 and 12 weeks). We also examined BDNF mRNA expression and protein levels at an intermediate age (8-10 weeks). We found that, regardless of age or sex, BDNF and TrkB protein levels did not differ between wild type and ZnT3 knockout mice. There were sex-specific differences in BDNF protein and mRNA expression, however. BDNF protein levels increased with age in female mice but not in males. And in females, but not males, ZnT3 KO mice exhibited great hippocampal BDNF mRNA expression than wild type mice. We conclude that, at least in naïve mice housed under standard laboratory conditions, elimination of vesicular zinc does not affect BDNF or TrkB protein levels.

Brain-derived neurotrophic factor is associated with coronary macrophage infiltrates in patients with acute coronary syndrome

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
R.A Montone ◽  
M Camilli ◽  
M Russo ◽  
M Del Buono ◽  
F Gurguglione ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
Neurotrophic Factor ◽  
Serum Levels ◽  
Brain Derived Neurotrophic Factor ◽  
C Reactive Protein ◽  
St Segment Elevation ◽  
Protein Levels ◽  
Reactive Protein ◽  
Coronary Syndrome ◽  
St Segment

Abstract Background Brain-derived neurotrophic factor (BDNF) is a neurotrophine that plays a key role in the regulation of both central and peripheral nervous system. Moreover, BDNF is secreted in multiple tissues and exerts systemic, autocrine, and paracrine effects in the cardiovascular system. Of importance, BDNF expression was enhanced in macrophages and smooth muscle cells in atherosclerotic coronary arteries and may be involved in thrombus formation. Thus, BDNF has been suggested as an important link between inflammation and thrombosis, potentially involved in the pathogenesis of acute coronary syndrome (ACS). Purpose In our study we aimed at assessing serum levels of BDNF in patients with ACS, evaluating differences according to clinical presentation [ST-segment elevation myocardial infarction (STEMI) vs. Non-ST-segment elevation ACS (NSTE-ACS)]. Moreover, we assessed the presence of optical coherence (OCT)-defined macrophage infiltrates (MØI) in the culprit vessel of ACS patients and evaluated their relationship with BDNF levels. Methods ACS patients were prospectively selected. Blood samples were collected at admission and serum levels of BDNF were subsequently assessed. Presence of OCT-defined MØI along the culprit vessel was assessed. Results 166 ACS patients were enrolled [mean age 65.3±11.9 years, 125 (75.3%) male, 109 STEMI, 57 NSTE-ACS]. Serum levels of BDNF were higher among STEMI patients compared with NSTE-ACS [median (IQR) 2.48 pg/mL (1.54–3.34) vs. 2.12 pg/mL (1.34–2.47), p=0.007], while C-reactive protein levels did not differ between the two groups. OCT assessment was performed in 53 patients and MØI were detected in 27 patients. Of importance, patients with MØI in the culprit vessel had higher levels of BDNF compared with patients without MØI [median (IQR) 2.23 pg/mL (1.38–2.53) vs. 1.41 pg/mL (0.93–2.07), p=0.023], while C-reactive protein levels did not differ between the two groups. Of note, at multivariate regression analysis BDNF levels were independent predictor of MØI [OR: 2.20; 95% CI (1.02–4.74), p=0.043]. Conclusions Serum levels of BDNF may reliable identify the presence of local macrophage inflammatory infiltrates in patients with ACS. Moreover, BDNF levels are higher in patients with STEMI compared with NSTE-ACS. Taken together, these data suggest that BDNF may represent an interesting link between local inflammatory activation and enhanced thrombosis in ACS. BDNF serum levels Funding Acknowledgement Type of funding source: None

Role of brain-derived neurotrophic factor in the control of D3 receptor expression

1999 ◽  
Vol 9 ◽  
pp. 184-185 ◽  
Author(s):  
O. Guillin ◽  
L. Damier ◽  
N. Griffon ◽  
J. Diaz ◽  
P. Carroll ◽  
...  
Keyword(s):  
Neurotrophic Factor ◽  
Brain Derived Neurotrophic Factor ◽  
Receptor Expression ◽  
D3 Receptor

scholarly journals Brain-derived neurotrophic factor enhances spontaneous sleep in rats and rabbits

1999 ◽  
Vol 276 (5) ◽  
pp. R1334-R1338 ◽  
Author(s):  
Tetsuya Kushikata ◽  
Jidong Fang ◽  
James M. Krueger
Keyword(s):  
Growth Factors ◽  
Neurotrophic Factor ◽  
Brain Temperature ◽  
Brain Derived Neurotrophic Factor ◽  
Normal Brain ◽  
Sprague Dawley ◽  
Sleep Regulation ◽  
Bdnf Mrna ◽  
Sprague Dawley Rats ◽  
Intracerebroventricular Injections

Various growth factors are involved in sleep regulation. Brain-derived neurotrophic factor (BDNF) belongs to the neurotrophin family; it and its receptors are found in normal brain. Furthermore, cerebral cortical levels of BDNF mRNA have a diurnal variation and increase after sleep deprivation. Therefore, we investigated whether BDNF would promote sleep. Twenty-four male Sprague-Dawley rats (320–380 g) and 25 male New Zealand White rabbits (4.5–5.5 kg) were surgically implanted with electroencephalographic (EEG) electrodes, a brain thermistor, and a lateral intracerebroventricular cannula. The animals were injected intracerebroventricularly with pyrogen-free saline and, on a separate day, one of the following doses of BDNF: 25 or 250 ng in rabbits; 10, 50, or 250 ng in rats. The EEG, brain temperature, and motor activity were recorded for 23 h after the intracerebroventricular injections. BDNF increased time spent in non-rapid eye movement sleep (NREMS) in rats and rabbits and REMS in rabbits. Current results provide further evidence that various growth factors are involved in sleep regulation.

Dose-related effects of venlafaxine on pCREB and brain-derived neurotrophic factor (BDNF) in the hippocampus of the rat by chronic unpredictable stress

2011 ◽  
Vol 23 (1) ◽  
pp. 20-30 ◽  
Author(s):  
Jing-Jing Li ◽  
Yong-Gui Yuan ◽  
Gang Hou ◽  
Xiang-Rong Zhang
Keyword(s):  
Neurotrophic Factor ◽  
Sucrose Solution ◽  
Brain Derived Neurotrophic Factor ◽  
Rat Hippocampus ◽  
Antidepressant Effect ◽  
High Dose ◽  
Sprague Dawley ◽  
Bdnf Mrna ◽  
Adult Rat ◽  
Element Binding Protein

Background: The molecular pathogenesis of depression and psychopharmacology of antidepressants remain elusive. Recent hypotheses suggest that changes in neurogenesis and plasticity may underlie the aetiology of depression. The hippocampus is affected by depression and shows neuronal remodelling during adulthood.Objective: The present study on the adult rat hippocampus, was to evaluate the dose-related effects of chronic venlafaxine on the expression of brain-derived neurotrophic factor (BDNF) and phosphorylated cyclic-AMP response element binding protein (pCREB).Methods: Sprague-Dawley rats were exposed to a variety of chronic unpredictable stressors (CUSs) to establish a depression model. Rats were treated for either 14 or 28 days with venlafaxine (5 and 10 mg/kg, respectively). The hippocampal expression of pCREB and BDNF mRNA and protein was assessed by using immunohistochemistry, western blotting and reverse transcription polymerase chain reaction (RT-PCR).Results: Rats subjected to CUS procedure consumed less sucrose solution compared with non-stressed rats. The CUS influenced exploratory activity resulting in a reduction of the motility counts. Chronic low dose (5 mg/kg, 14 and 28 days), but not high dose (10 mg/kg, 14 and 28 days) of venlafaxine treatment increased the expression of pCREB and BDNF mRNA and protein in the CUS rat hippocampus.Conclusion: Neuronal plasticity-associated proteins such as pCREB and BDNF play an important role both in stress-related depression and in antidepressant effect.

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