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https://www.readbyqxmd.com/read/28098876/bdnf-regulates-the-expression-and-secretion-of-vegf-from-osteoblasts-via-the-trkb-erk1-2-signaling-pathway-during-fracture-healing
#1
Zitao Zhang, Yan Zhang, Zhengnan Zhou, Hongfei Shi, Xusheng Qiu, Jin Xiong, Yixin Chen
Brain‑derived neurotrophic factor (BDNF), a member of the neurotropic family, is expressed in osteoblast‑like cells of a fracture callus, however, its role in fracture healing remains to be fully elucidated. Osteoblasts isolated from Sprague Dawley rats were stimulated by BDNF in a dose‑ and time‑dependent manner. Immunoblotting and immunofluorescence was used to detect the expression and distribution of targeted proteins. The concentration of vascular endothelial growth factor (VEGF) released in medium was determined using an ELISA...
January 12, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28098423/brain-derived-neurotrophic-factor-attenuates-doxorubicin-induced-cardiac-dysfunction-through-activating-akt-signalling-in-rats
#2
Pengzhou Hang, Jing Zhao, Li Sun, Minghui Li, Yu Han, Zhimin Du, Yue Li
The clinical application of doxorubicin (Dox) is limited by its adverse effect of cardiotoxicity. Previous studies have suggested the cardioprotective effect of brain-derived neurotrophic factor (BDNF). We hypothesize that BDNF could protect against Dox-induced cardiotoxicity. Sprague Dawley rats were injected with Dox (2.5 mg/kg, 3 times/week, i.p.), in the presence or absence of recombinant BDNF (0.4 μg/kg, i.v.) for 2 weeks. H9c2 cells were treated with Dox (1 μM) and/or BDNF (400 ng/ml) for 24 hrs. Functional roles of BDNF against Dox-induced cardiac injury were examined both in vivo and in vitro...
November 7, 2016: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28097465/hydroxysafflor-yellow-a-improves-motor-dysfunction-in-the-rotenone-induced-mice-model-of-parkinson-s-disease
#3
Tian Wang, Lijie Wang, Cuiting Li, Bing Han, Zhenhua Wang, Ji Li, Yan Lv, Shuyun Wang, Fenghua Fu
Dopamine D3 receptor (DRD3) is diminished in patients of Parkinson's disease (PD). Brain-derived neurotrophic factor (BDNF) is responsible for regulating expression of the DRD3 in the brain. Our previous study showed that hydroxysafflor yellow A (HSYA) could increase BDNF content in the striatum of PD mice. This experiment aimed to evaluate whether HSYA can improve the motor dysfunction induced by rotenone through regulating the BDNF/TrkB/DRD3 signaling pathway in mice. Male C57/BL6 mice were intraperitoneally treated with HSYA...
January 17, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28072837/locally-produced-bdnf-promotes-sclerotic-change-in-alveolar-bone-after-nerve-injury
#4
Hiroko Ida-Yonemochi, Yurie Yamada, Hiroyuki Yoshikawa, Kenji Seo
Brain-derived neurotrophic factor (BDNF), which is released due to nerve injury, is known to promote the natural healing of injured nerves. It is often observed that damage of mandibular canal induces local sclerotic changes in alveolar bone. We reported that peripheral nerve injury promotes the local production of BDNF; therefore, it was possible to hypothesize that peripheral nerve injury affects sclerotic changes in the alveolar bone. This study aimed to evaluate the effect of BDNF on osteogenesis using in vitro osteoblast-lineage cell culture and an in vivo rat osteotomy model...
2017: PloS One
https://www.readbyqxmd.com/read/28070119/ocd-like-behavior-is-caused-by-dysfunction-of-thalamo-amygdala-circuits-and-upregulated-trkb-erk-mapk-signaling-as-a-result-of-spred2-deficiency
#5
M Ullrich, M Weber, A M Post, S Popp, J Grein, M Zechner, H Guerrero González, A Kreis, A G Schmitt, N Üçeyler, K-P Lesch, K Schuh
Obsessive-compulsive disorder (OCD) is a common neuropsychiatric disease affecting about 2% of the general population. It is characterized by persistent intrusive thoughts and repetitive ritualized behaviors. While gene variations, malfunction of cortico-striato-thalamo-cortical (CSTC) circuits, and dysregulated synaptic transmission have been implicated in the pathogenesis of OCD, the underlying mechanisms remain largely unknown. Here we show that OCD-like behavior in mice is caused by deficiency of SPRED2, a protein expressed in various brain regions and a potent inhibitor of Ras/ERK-MAPK signaling...
January 10, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28053596/celecoxib-enhances-anticancer-effect-of-cisplatin-and-induces-anoikis-in-osteosarcoma-via-pi3k-akt-pathway
#6
Bing Liu, Shigui Yan, Liyan Qu, Jian Zhu
BACKGROUND: COX-2, an inducible enzyme, is associated with inflammatory diseases and carcinogenesis. Overexpression of COX-2 occurs in many human malignancies, including osteosarcoma. COX-2 positivity is form 67 to 92% in osteosarcoma, and COX-2 expresses 141-fold more in cancer stem cell spheres than daughter adherent cells. In our study, we have reported that celecoxib, a cyclooxygenase-2 inhibitor, induces apoptosis in human osteosarcoma cell line MG-63 via down-regulation of PI3K/Akt...
2017: Cancer Cell International
https://www.readbyqxmd.com/read/28043792/generation-of-a-novel-artificial-trkb-agonist-bm17d99-using-t7-phage-displayed-random-peptide-libraries
#7
Toshiyuki Ohnishi, Kotaro Sakamoto, Asano Asami-Odaka, Kimie Nakamura, Ayako Shimizu, Takashi Ito, Taiji Asami, Tetsuya Ohtaki, Hiroshi Inooka
Tropomyosin receptor kinase B (TrkB) is a known receptor of brain-derived neurotrophic factor (BDNF). Because it plays a critical role in the regulation of neuronal development, maturation, survival, etc., TrkB is a good target for drugs against central nervous system diseases. In this study, we aimed to generate peptidic TrkB agonists by applying random peptide phage display technology. After the phage panning against recombinant Fc-fused TrkB (TrkB-Fc), agonistic phages were directly screened against TrkB-expressing HEK293 cells...
December 30, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28039433/structural-characterization-of-nonactive-site-trka-selective-kinase-inhibitors
#8
Hua-Poo Su, Keith Rickert, Christine Burlein, Kartik Narayan, Marina Bukhtiyarova, Danielle M Hurzy, Craig A Stump, Xufang Zhang, John Reid, Alicja Krasowska-Zoladek, Srivanya Tummala, Jennifer M Shipman, Maria Kornienko, Peter A Lemaire, Daniel Krosky, Amanda Heller, Abdelghani Achab, Chad Chamberlin, Peter Saradjian, Berengere Sauvagnat, Xianshu Yang, Michael R Ziebell, Elliott Nickbarg, John M Sanders, Mark T Bilodeau, Steven S Carroll, Kevin J Lumb, Stephen M Soisson, Darrell A Henze, Andrew J Cooke
Current therapies for chronic pain can have insufficient efficacy and lead to side effects, necessitating research of novel targets against pain. Although originally identified as an oncogene, Tropomyosin-related kinase A (TrkA) is linked to pain and elevated levels of NGF (the ligand for TrkA) are associated with chronic pain. Antibodies that block TrkA interaction with its ligand, NGF, are in clinical trials for pain relief. Here, we describe the identification of TrkA-specific inhibitors and the structural basis for their selectivity over other Trk family kinases...
January 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28032807/region-specific-expression-of-precursor-and-mature-brain-derived-neurotrophic-factors-after-chronic-alcohol-exposure
#9
Jin-Wei Yang, Wei Ma, Yan-Lei Yang, Xian-Bin Wang, Xing-Tong Li, Tong-Tong Wang, Xiang-Peng Wang, Wei Gao, Jun-Yan Li, Xin-Fu Zhou, Jian-Hui Guo, Li-Yan Li
BACKGROUND: Alcohol abuse is a serious health problem worldwide that causes a variety of physical and mental disorders. Research has shown that the brain-derived neurotrophic factor (BDNF) plays an important role in alcohol addiction. The BDNF precursor (proBDNF) exhibits different actions than BDNF through separate receptors and pathways in the central nervous system. However, the effects of proBDNF and BDNF in alcohol addiction are not fully known. OBJECTIVES: The objective was to identify the expression patterns and effects of proBDNF and BDNF after chronic alcohol exposure...
December 29, 2016: American Journal of Drug and Alcohol Abuse
https://www.readbyqxmd.com/read/28027399/activation-of-bdnf-trkb-signaling-in-the-pedunculopontine-tegmental-nucleus-ppt-a-novel-mechanism-for-the-homeostatic-regulation-of-rem-sleep
#10
Abigail K Barnes, Richa Koul-Tiwari, Jennifer M Garner, Phillip A Geist, Subimal Datta
REM sleep dysregulation is a symptom of many neuropsychiatric disorders, yet the mechanisms of REM sleep homeostatic regulation are not fully understood. We have shown that, after REM sleep deprivation, the pedunculopontine tegmental nucleus (PPT) plays a critical role in the generation of recovery REM sleep. In the present study, we used multidisciplinary techniques to show a causal relationship between BDNF-TrkB signaling in the PPT and the development of REM sleep homeostatic drive. Rats were randomly assigned to conditions of unrestricted sleep or selective REM sleep deprivation (RSD) with PPT microinjections of vehicle control or a dose of a TrkB receptor inhibitor (2, 3, or 4 nmol K252a or 4 nmol ANA-12)...
December 27, 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28025992/mir-124-promotes-the-neuronal-differentiation-of-mouse-inner-ear-neural-stem-cells
#11
Di Jiang, Jintao Du, Xuemei Zhang, Wei Zhou, Lin Zong, Chang Dong, Kaitian Chen, Yu Chen, Xihui Chen, Hongyan Jiang
MicroRNAs (miRNAs or miRs) act as key regulators in neuronal development, synaptic morphogenesis and plasticity. However, their role in the neuronal differentiation of inner ear neural stem cells (NSCs) remains unclear. In this study, 6 miRNAs were selected and their expression patterns during the neuronal differentiation of inner ear NSCs were examined by RT-qPCR. We demonstrated that the culture of spiral ganglion stem cells present in the inner ears of newborn mice gave rise to neurons in vitro. The expression patterns of miR‑124, miR‑132, miR‑134, miR‑20a, miR‑17-5p and miR‑30a-5p were examined during a 14-day neuronal differentiation period...
November 2016: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28012455/maternal-obesity-alters-brain-derived-neurotrophic-factor-bdnf-signaling-in-the-placenta-in-a-sexually-dimorphic-manner
#12
Calais S Prince, Alina Maloyan, Leslie Myatt
INTRODUCTION: Obesity is a major clinical problem in obstetrics being associated with adverse pregnancy outcomes and fetal programming. Brain derived neurotrophic factor (BDNF), a validated miR-210 target, is necessary for placental development, fetal growth, glucose metabolism, and energy homeostasis. Plasma BDNF levels are reduced in obese individuals; however, placental BDNF has yet to be studied in the context of maternal obesity. In this study, we investigated the effect of maternal obesity and sexual dimorphism on placental BDNF signaling...
January 2017: Placenta
https://www.readbyqxmd.com/read/28012173/trpc3-channels-play-a-critical-role-in-the-theta-component-of-pilocarpine-induced-status-epilepticus-in-mice
#13
Kevin D Phelan, U Thaung Shwe, Michael A Cozart, Hong Wu, Matthew M Mock, Joel Abramowitz, Lutz Birnbaumer, Fang Zheng
OBJECTIVE: Canonical transient receptor potential (TRPC) channels constitute a family of cation channels that exhibit a regional and cell-specific expression pattern throughout the brain. It has been reported previously that TRPC3 channels are effectors of the brain-derived neurotrophic factor (BDNF)/trkB signaling pathway. Given the long postulated role of BDNF in epileptogenesis, TRPC3 channels may be a critical component in the underlying pathophysiology of seizure and epilepsy. In this study, we investigated the precise role of TRPC3 channels in pilocarpine-induced status epilepticus (SE)...
December 24, 2016: Epilepsia
https://www.readbyqxmd.com/read/28005701/effect-of-short-term-exercise-training-on-brain-derived-neurotrophic-factor-signaling-in-spontaneously-hypertensive-rats
#14
Alice Monnier, Philippe Garnier, Aurore Quirie, Nicolas Pernet, Céline Demougeot, Christine Marie, Anne Prigent-Tessier
OBJECTIVE: Decreased brain-derived neurotrophic factor (BDNF) level has been reported in the hippocampus of hypertensive rats. The present study explored whether brain neurons and/or endothelial cells are targeted by hypertension with respect to BDNF expression and the potential of physical exercise to cope with hypertension. METHODS: Physical exercise was induced in spontaneously hypertensive rats (SHR) and Wistar Kyoto (WKY) rats. The hippocampus of sedentary and exercised rats (n = 6 for each group) were used for western blots to assess proBDNF, mature BDNF (mBDNF), tropomyosin-related kinase B (TrkB), P-TrkB (TrkB phosphorylated at tyrosine 816), synaptophysin, endothelial nitric oxide synthase (eNOS) and eNOS phosphorylated at serine 1177 protein levels...
February 2017: Journal of Hypertension
https://www.readbyqxmd.com/read/28004953/phosphorylation-of-tyrosine-receptor-kinase-b-in-the-dorsal-striatum-and-dorsal-hippocampus-is-associated-with-response-learning-in-a-water-plus-maze
#15
Amanda R Pahng, Paul J Colombo
The dorsal hippocampus and dorsal striatum have dissociable roles in learning and memory that are related to region-specific changes in proteins necessary for neuronal plasticity and memory formation. There is additional evidence that the hippocampus and striatum can interact during memory formation. Phosphorylation of tyrosine receptor kinase B is important for memory formation in the hippocampus, but whether or not it has a role in striatum-dependent learning, or in interactions between the hippocampus and striatum, has not been examined...
December 22, 2016: Behavioral Neuroscience
https://www.readbyqxmd.com/read/28003751/effect-of-dexmedetomidine-on-hippocampal-neuron-development-and-bdnf-trkb-signal-expression-in-neonatal-rats
#16
Jie Lv, Wei Ou, Xiao-Hua Zou, Yin Yao, Jin-Li Wu
The study aimed to explore the effect of dexmedetomidine (DEX) on hippocampal neuron development process and on molecular expression of brain-derived neurotrophic factor (BDNF)-tyrosine receptor kinase B (TrkB) signaling pathway in neonatal rats. The hippocampal neuron cells were isolated from newborn neonatal rats and cultured in vitro. One control group and three treated groups with 1, 10, and 100 μmol/L DEX were used for the study. Cell activity and apoptosis were detected by the MTT and terminal deoxynucleotidyl transferase-mediated biotinylated uridine triphosphate (UTP) nick end labeling assays...
2016: Neuropsychiatric Disease and Treatment
https://www.readbyqxmd.com/read/28002846/unchanged-neurotrophic-factors-and-their-receptors-correlate-with-sparing-in-extraocular-muscles-in-amyotrophic-lateral-sclerosis
#17
Vahid M Harandi, Aida R N Gaied, Thomas Brännström, Fatima Pedrosa Domellöf, Jing-Xia Liu
Purpose: To investigate the impact of amyotrophic lateral sclerosis (ALS) on the extraocular muscles (EOMs) by examining the distribution of neurotrophic factors (NTFs) and their receptors in EOMs and limb muscles from ALS transgenic mice. Methods: Muscle samples collected from transgenic mice overexpressing human superoxide dismutase type 1 mutations (SOD1G93A, the most widely used mouse model of ALS) at 50 and 150 days as well as age-matched controls were analyzed with immunohistochemistry using antibodies against brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), neurotrophin-4/5 (NT-4), glial cell line-derived neurotrophic factor (GDNF), and the neurotrophin receptors p75NTR, tyrosine kinase (Trk) receptor TrkB and TrkC, and GDNF family receptor alpha-1 (GFRα-1)...
December 1, 2016: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/27998780/paternal-deprivation-affects-social-behaviors-and-neurochemical-systems-in-the-offspring-of-socially-monogamous-prairie-voles
#18
Manal Tabbaa, Kelly Lei, Yan Liu, Zuoxin Wang
Early life experiences, particularly the experience with parents, are crucial to phenotypic outcomes in both humans and animals. Although the effects of maternal deprivation on offspring well-being have been studied, paternal deprivation (PD) has received little attention despite documented associations between father absence and children health problems in humans. In the present study, we utilized the socially monogamous prairie vole (Microtus ochrogaster), which displays male-female pair bonding and bi-parental care, to examine the effects of PD on adult behaviors and neurochemical expression in the hippocampus...
December 18, 2016: Neuroscience
https://www.readbyqxmd.com/read/27995523/in-vitro-modulation-of-trkb-receptor-signaling-upon-sequential-delivery-of-curcumin-dha-loaded-carriers-towards-promoting-neuronal-survival
#19
Luis P B Guerzoni, Valérie Nicolas, Angelina Angelova
PURPOSE: To in vitro investigate the capacity of carrier-free and lipid-nanoparticle (NP)-encapsulated phytochemical compounds to prevent neuronal damage through neurotrophin potentiating activities. Delivery of molecules promoting the neurotrophin receptor signaling in the central nervous system (CNS) present ongoing interest for combination therapy development. METHODS: Super-resolution Stimulated Emission Depletion (STED) microscopy imaging and flow cytometry analysis were employed to study the expression of the neurotrophin TrkB receptor in a neuronal cell model, which is highly responsive to binding of brain-derived neurotrophic factor (BDNF)...
December 19, 2016: Pharmaceutical Research
https://www.readbyqxmd.com/read/27992087/urokinase-type-plasminogen-activator-modulates-mammalian-circadian-clock-phase-regulation-in-tissue-type-plasminogen-activator-knockout-mice
#20
Joanna M Cooper, Ashutosh Rastogi, Jessica A Krizo, Eric M Mintz, Rebecca A Prosser
Glutamate phase shifts the circadian clock in the mammalian suprachiasmatic nucleus (SCN) by activating NMDA receptors. Tissue-type plasminogen activator (tPA) gates phase shifts by activating plasmin to generate m(ature)BDNF, which binds TrkB receptors allowing clock phase shifts. Here we investigate phase shifting in tPA knockout (tPA(-/-) ; B6.129S2-Plat(tm1Mlg) /J) mice, and identify urokinase-type plasminogen activator (uPA) as an additional circadian clock regulator. Behavioral activity rhythms in tPA(-/-) mice entrain to a light-dark (LD) cycle and phase shift in response to nocturnal light pulses with no apparent loss in sensitivity...
December 19, 2016: European Journal of Neuroscience
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