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.

No effect of escitalopram versus placebo on brain-derived neurotrophic factor in healthy individuals: a randomised trial

2015 ◽  
Vol 28 (2) ◽  
pp. 101-109 ◽  
Author(s):  
Ulla Knorr ◽  
Pernille Koefoed ◽  
Mia H. Greisen Soendergaard ◽  
Maj Vinberg ◽  
Ulrik Gether ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Whole Blood ◽  
Neurotrophic Factor ◽  
Messenger Rna ◽  
Randomised Trial ◽  
Significant Negative Correlation ◽  
Brain Derived Neurotrophic Factor ◽  
Healthy Individuals ◽  
Bdnf Mrna ◽  
Significant Difference

ObjectiveBrain-derived neurotrophic factor (BDNF) seems to play an important role in the course of depression including the response to antidepressants in patients with depression. We aimed to study the effect of an antidepressant intervention on peripheral BDNF in healthy individuals with a family history of depression.MethodsWe measured changes in BDNF messenger RNA (mRNA) expression and whole-blood BDNF levels in 80 healthy first-degree relatives of patients with depression randomly allocated to receive daily tablets of escitalopram 10 mg versus placebo for 4 weeks.ResultsWe found no statistically significant difference between the escitalopram and the placebo group in the change in BDNF mRNA expression and whole-blood BDNF levels. Post hoc analyses showed a statistically significant negative correlation between plasma escitalopram concentration and change in whole-blood BDNF levels in the escitalopram-treated group.ConclusionThe results of this randomised trial suggest that escitalopram 10 mg has no effect on peripheral BDNF levels in healthy individuals.

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.

Photochemical stroke and brain-derived neurotrophic factor (BDNF) mRNA expression

Neuroreport ◽  
1992 ◽  
Vol 3 (6) ◽  
pp. 473-476 ◽  
Author(s):  
Maria Cristina Comelli ◽  
Maria Serena Seren ◽  
Diego Guidolin ◽  
Radmila M. Manev ◽  
Marco Favaron ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Neurotrophic Factor ◽  
Brain Derived Neurotrophic Factor ◽  
Bdnf Mrna

scholarly journals Absence of Thyroid Hormone Induced Delayed Dendritic Arborization in Mouse Primary Hippocampal Neurons Through Insufficient Expression of Brain-Derived Neurotrophic Factor

2021 ◽  
Vol 12 ◽  
Author(s):  
Hiroyuki Yajima ◽  
Izuki Amano ◽  
Sumiyasu Ishii ◽  
Tetsushi Sadakata ◽  
Wataru Miyazaki ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Neurotrophic Factor ◽  
Hippocampal Neurons ◽  
Brain Derived Neurotrophic Factor ◽  
Mrna Levels ◽  
Protein Levels ◽  
Primary Hippocampal Neurons ◽  
Developmental Impairment

Thyroid hormone (TH) plays important roles in the developing brain. TH deficiency in early life leads to severe developmental impairment in the hippocampus. However, the mechanisms of TH action in the developing hippocampus are still largely unknown. In this study, we generated 3,5,3’-tri-iodo-l-thyronine (T3)-free neuronal supplement, based on the composition of neuronal supplement 21 (NS21), to examine the effect of TH in the developing hippocampus using primary cultured neurons. Effects of TH on neurons were compared between cultures in this T3-free culture medium (-T3 group) and a medium in which T3 was added (+T3 group). Morphometric analysis and RT-qPCR were performed on 7, 10, and 14 days in vitro (DIV). On 10 DIV, a decreased dendrite arborization in -T3 group was observed. Such difference was not observed on 7 and 14 DIV. Brain-derived neurotrophic factor (Bdnf) mRNA levels also decreased significantly in -T3 group on 10 DIV. We then confirmed protein levels of phosphorylated neurotrophic tyrosine kinase type 2 (NTRK2, TRKB), which is a receptor for BDNF, on 10 DIV by immunocytochemistry and Western blot analysis. Phosphorylated NTRK2 levels significantly decreased in -T3 group compared to +T3 group on 10 DIV. Considering the role of BDNF on neurodevelopment, we examined its involvement by adding BDNF on 8 and 9 DIV. Addition of 10 ng/ml BDNF recovered the suppressed dendrite arborization induced by T3 deficiency on 10 DIV. We show that the lack of TH induces a developmental delay in primary hippocampal neurons, likely caused through a decreased Bdnf expression. Thus, BDNF may play a role in TH-regulated dendritogenesis.

scholarly journals Induction of the plasticity-associated immediate early gene Arc by stress and hallucinogens: role of brain-derived neurotrophic factor

2012 ◽  
Vol 16 (2) ◽  
pp. 405-415 ◽  
Author(s):  
Madhurima Benekareddy ◽  
Amrita R. Nair ◽  
Brian G. Dias ◽  
Deepika Suri ◽  
Anita E. Autry ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Knockout Mice ◽  
Neurotrophic Factor ◽  
Immobilization Stress ◽  
Immediate Early Gene ◽  
Brain Derived Neurotrophic Factor ◽  
Early Gene ◽  
Immediate Early ◽  
Trophic Factor ◽  
Mrna Levels

Abstract Exposure to stress and hallucinogens in adulthood evokes persistent alterations in neurocircuitry and emotional behaviour. The structural and functional changes induced by stress and hallucinogen exposure are thought to involve transcriptional alterations in specific effector immediate early genes. The immediate early gene, activity regulated cytoskeletal-associated protein (Arc), is important for both activity and experience dependent plasticity. We sought to examine whether trophic factor signalling through brain-derived neurotrophic factor (BDNF) contributes to the neocortical regulation of Arc mRNA in response to distinct stimuli such as immobilization stress and the hallucinogen 2,5-dimethoxy-4-iodoamphetamine (DOI). Acute exposure to either immobilization stress or DOI induced Arc mRNA levels within the neocortex. BDNF infusion into the neocortex led to a robust up-regulation of local Arc transcript expression. Further, baseline Arc mRNA expression in the neocortex was significantly decreased in inducible BDNF knockout mice with an adult-onset, forebrain specific BDNF loss. The induction of Arc mRNA levels in response to both acute immobilization stress or a single administration of DOI was significantly attenuated in the inducible BDNF knockout mice. Taken together, our results implicate trophic factor signalling through BDNF in the regulation of cortical Arc mRNA expression, both under baseline conditions and following stress and hallucinogen exposure. These findings suggest the possibility that the regulation of Arc expression via BDNF provides a molecular substrate for the structural and synaptic plasticity observed following stimuli such as stress and hallucinogens.

Abstract TP268: Induction Profile of Mesencephalic Astrocyte-derived Neurotrophic Factor by Cerebral Ischemia and its Implication for Neuroprotection

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Ludmila Belayev ◽  
Sung-Ha Hong ◽  
Pranab K Mukherjee ◽  
Hemant Menghani ◽  
Larissa Khoutorova ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Dentate Gyrus ◽  
Mrna Expression ◽  
Neurotrophic Factor ◽  
Focal Cerebral Ischemia ◽  
Artery Occlusion ◽  
Ischemic Penumbra ◽  
Protein Levels

Introduction: Mesencephalic astrocyte-derived neurotrophic factor (MANF) has been identified as a secretion protein, which biases immune cells toward an anti-inflammatory phenotype, thereby promoting tissue repair after various injuries to neurons in vivo or in vitro. However, the function of MANF during and after brain ischemia is still not known. The purpose of our study was to examine the characteristics and implication of MANF expression induced by focal cerebral ischemia. In addition we investigated if docosahexaenoic acid (DHA) potentiates MANF mRNA expression and provides additional neuroprotection. Methods: Male SD (280-320) rats were anesthetized with isoflurane and subjected to 2 h of middle cerebral artery occlusion (MCAo) by intraluminal suture. DHA (5 mg/kg; n=13) or vehicle (saline; n=8) was administered IV at 3 h after the onset of MCAo. Neurological function was evaluated during occlusion (60 min) and on days 1, 3 and 7 after MCAo. MANF mRNA expression, protein levels, and apoptosis were measured by immunohistochemistry and Western blotting. Results: Behavioral deficit was significantly improved by treatment with DHA compared to vehicle on days 1, 3 and 7. MANF was found to be extremely upregulated in the ischemic penumbra. The expression of MANF was neuronal in the cortex and dentate gyrus. DHA administration significantly increased the number of MANF + /NeuN + cells in the cortex (by 76.6 %) and dentate gyrus (by 20.5 %) compared to saline-treated animals. The number of MANF/NeuN-positive cells was not different in the subcortex, CA1 and CA3 regions between DHA- and saline-treated groups. Treatment with DHA increased MANF + /GFAP + cells in the subcortex (by 27.7 %) and dentate gyrus (by 38.0 %) compared to the vehicle-treated brains. Total and cortical infarct volumes were attenuated by DHA treatment by 48 % and by 73 % compared to vehicle treatment at 24 h after MCAo. Conclusion: MANF mRNA expression and protein levels are increased after focal cerebral ischemia. It was found to be extremely upregulated in the ischemic penumbra and dentate gyrus. The expression of MANF was mostly neuronal and astrocytic. DHA potentiates MANF expression and provides additional neuroprotection.

scholarly journals Brain-derived neurotrophic factor, epigenetics in stroke skeletal muscle, and exercise training

2019 ◽  
Vol 5 (3) ◽  
pp. e331 ◽  
Author(s):  
Alice S. Ryan ◽  
Huichun Xu ◽  
Frederick M. Ivey ◽  
Richard F. Macko ◽  
Charlene E. Hafer-Macko
Keyword(s):  
Skeletal Muscle ◽  
Dna Methylation ◽  
Exercise Training ◽  
Mrna Expression ◽  
Neurotrophic Factor ◽  
Methylation Status ◽  
Brain Derived Neurotrophic Factor ◽  
Vastus Lateralis Muscle ◽  
Bdnf Mrna ◽  
Blood Draw

Objective(1) To compare paretic (P) vs nonparetic (NP) skeletal muscle brain-derived neurotrophic factor (BDNF) and the effects of resistive training (RT) on systemic and skeletal muscle BDNF mRNA expression in stroke; and (2) to compare the DNA methylation profile for BDNF and BDNFAS (BDNF antisense RNA) between P and NP muscle and the effects of aerobic exercise training (AEX) on DNA methylation in stroke.MethodsIn this longitudinal investigation, participants (50–76 years) with chronic stroke underwent a fasting blood draw, a 12-week (3×/week) RT intervention (n = 16), and repeated bilateral vastus lateralis muscle tissue biopsies (n = 10) with BDNF expression determined by RT-PCR. Five stroke survivors completed 6 months of AEX (3×/week) and had bilateral muscle biopsies. DNA methylation status in gene BDNF and BDNFAS was assessed by Illumina 450k methylation array.ResultsP muscle had ∼45% lower BDNF mRNA expression than NP muscle (6.79 ± 1.30 vs 10.52 ± 2.06 arbitrary units [AU], p < 0.05), and P muscle exhibited differential methylation status in the DNA sequences of BDNF (3 CpG [5′-C-phosphate-G-3′] sites, p = 0.016–0.044) and BDNFAS (1 CpG site, p = 0.016) compared to NP. Plasma BDNF and muscle BDNF messenger RNA (mRNA) expression did not significantly change after RT. BDNFAS DNA methylation increased after AEX in P relative to NP muscle (p = 0.017).ConclusionsThis is the first evidence that stroke hemiparesis reduces BDNF skeletal muscle expression, with our findings identifying methylation alterations on the DNA sequence of BDNF and BDNFAS gene. Preliminary results further indicate that AEX increases methylation in BDNFAS gene, which presumably could regulate the expression of BDNF.

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