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brain-derived neurotrophic factor

Marion T Turnbull, Elizabeth J Coulson
Alzheimer's disease (AD) is a progressive, irreversible neurodegenerative disease that destroys memory and cognitive function. Aggregates of hyperphosphorylated tau protein are a prominent feature in the brain of patients with AD, and are a major contributor to neuronal toxicity and disease progression. However, the factors that initiate the toxic cascade that results in tau hyperphosphorylation in sporadic AD are unknown. Here we investigated whether degeneration of basal forebrain cholinergic neurons (BFCNs) and/or a resultant decrease in neurotrophin signaling cause aberrant tau hyperphosphorylation...
October 20, 2016: Journal of Alzheimer's Disease: JAD
Sarah Elizabeth Skerratt, Mark D Andrews, Sharan K Bagal, James Bilsland, David Brown, Peter J Bungay, Susan Cole, Karl R Gibson, Russell Jones, Inaki Morao, Angus Nedderman, Kiyoyuki Omoto, Colin Robinson, Thomas Ryckmans, Kimberly Skinner, Paul Anthony Stupple, Gareth Waldron
The neurotrophin family of growth factors, comprised of nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), neurotrophin 3 (NT3) and neurotrophin 4 (NT4), is implicated in the physiology of chronic pain. Given the clinical efficacy of anti-NGF monoclonal antibody (mAb) therapies, there is significant interest in the development of small molecule modulators of neurotrophin activity. Neurotrophins signal through the tropomyosin related kinase (Trk) family of tyrosine kinase receptors, hence Trk kinase inhibition represents a potentially "druggable" point of intervention...
October 21, 2016: Journal of Medicinal Chemistry
Julia Vakhrusheva, Brielle Marino, T Scott Stroup, David Kimhy
Schizophrenia is characterized by extensive neurocognitive deficits, which are linked to greater disability, poorer functional outcome, and have been suggested to impact daily functioning more than clinical symptoms. Aerobic exercise (AE) has emerged as a potential intervention. This review examines the impact of AE on brain structure and function along with neurocognitive performance in individuals with schizophrenia. Preliminary evidence indicates that AE can increase hippocampal volume and cortical thickness, in addition to exerting a neuroprotective effect against hippocampal volume decrease and cortical thinning...
June 2016: Current Behavioral Neuroscience Reports
Chao Dong, Ji-Chun Zhang, Wei Yao, Qian Ren, Min Ma, Chun Yang, Shigeyuki Chaki, Kenji Hashimoto
BACKGROUND: Similar to the N-methyl-D-aspartate (NMDA) receptor antagonist ketamine, the metabotropic glutamate 2/3 (mGlu2/3) receptor antagonist, MGS0039 shows antidepressant effects. However, there are no reports comparing these two compounds in the social defeat stress model of depression. METHODS: We examined the effects of MGS0039 (1 mg/kg) and ketamine (10 mg/kg) on depression-like behavior in susceptible mice, after repeated social defeat stress. Protein levels of brain-derived neurotrophic factor (BDNF), TrkB, phospho-TrkB (p-TrkB), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor (GluA1) and postsynaptic density protein 95 (PSD-95), and dendritic spine density in selected brain regions were measured...
October 7, 2016: International Journal of Neuropsychopharmacology
Bok Soon Go, Sarah M Barry, Jacqueline F McGinty
Cocaine self-administration induces dysfunctional neuroadaptations in the prefrontal cortex that underlie relapse to cocaine-seeking. Cocaine self-administration disturbs glutamatergic transmission in the nucleus accumbens that is prevented by infusion of brain-derived neurotrophic factor (BDNF) into the prelimbic area of the prefrontal cortex. Intra-prelimbic infusion of BDNF decreases cocaine-seeking in a TrkB-ERK MAP kinase-dependent manner. Neuronal activity triggers an interaction between TrkB receptors and NMDA receptors, leading to ERK activation...
October 17, 2016: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
Mingyong Gao, Paul Lu, Dan Lynam, Bridget Bednark, W Marie Campana, Jeff Sakamoto, Mark Tuszynski
OBJECTIVE: We combined implantation of multi-channel templated agarose scaffolds with growth factor gene delivery to examine whether this combinatorial treatment can enhance peripheral axonal regeneration through long sciatic nerve gaps. APPROACH: 15 mm long scaffolds were templated into highly organized, strictly linear channels, mimicking the linear organization of natural nerves into fascicles of related function. Scaffolds were filled with syngeneic bone marrow stromal cells (MSCs) secreting the growth factor brain derived neurotrophic factor (BDNF), and lentiviral vectors expressing BDNF were injected into the sciatic nerve segment distal to the scaffold implantation site...
October 20, 2016: Journal of Neural Engineering
Poornapriya Ramamurthy, Joshua B White, Joong Yull Park, Richard I Hume, Fumi Ebisu, Flor Mendez, Shuichi Takayama, Kate F Barald
BACKGROUND: To send meaningful information to the brain, an inner ear cochlear implant (CI) must become closely coupled to as large and healthy a population of remaining Spiral Ganglion Neurons (SGN) as possible. Inner ear gangliogenesis depends on macrophage migration inhibitory factor (MIF), a directionally attractant neurotrophic cytokine made by both Schwann and supporting cells (Bank et al., 2012). MIF-induced mouse embryonic stem cell (mESC)-derived "neurons" could potentially substitute for lost or damaged SGN...
October 19, 2016: Developmental Dynamics: An Official Publication of the American Association of Anatomists
Hsin-An Chang, Ying-Hsiu Wang, Che-Se Tung, Chin-Bin Yeh, Yia-Ping Liu
OBJECTIVE: Brain-derived neurotrophic factor (BDNF) and its specific receptor, tropomyosin-related kinase (TrkB), play important roles in treating depression. In this experiment, we examined whether 7,8-dihydroxyflavone, a novel potent TrkB agonist, could reverse the behavioral and biochemical abnormalities induced by the chronic mild stress (CMS) paradigm in rats. METHODS: SD rats were exposed to a battery of stressors for 56 days. 7,8-dihydroxyflavone (5 and 20 mg/kg) were administered intraperitoneally during the last 28 days of the CMS paradigm...
September 2016: Psychiatry Investigation
Nam-In Kang, Jong-Il Park, Yong-Ku Kim, Jong-Chul Yang
OBJECTIVE: Brain-derived neurotrophic factor (BDNF), one of the most abundant and important neurotrophins, is known to be involved in the development, survival, maintenance, and plasticity of neurons in the nervous system. Some studies have suggested that BDNF may play a role in the pathophysiology of several psychiatric illnesses such as depression and schizophrenia. Similarly, it is likely that the alteration of BDNF may be associated with the neuro-modulation that contributes to the development of somatization disorder...
September 2016: Psychiatry Investigation
Onder Ozturk, Burge Kabukcu Basay, Ahmet Buber, Omer Basay, Huseyin Alacam, Ali Bacanlı, Şenay Görücü Yılmaz, Mehmet Emin Erdal, Hasan Herken, Eyup Sabri Ercan
OBJECTIVE: Attention-deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder that negatively affects different areas of life. We aimed to evaluate the associations between the Val66Met polymorphism of brain-derived neurotrophic factor (BDNF) and ADHD and to assess the effect of the BDNF polymorphism on the neurocognitive profile and clinical symptomatology in ADHD. METHODS: Two hundred one ADHD cases and 99 typically developing subjects (TD) between the ages of 8 and 15 years were involved in the study...
September 2016: Psychiatry Investigation
Hang Xu, Yu Zhang, Fan Zhang, San-Na Yuan, Feng Shao, Weiwen Wang
Early stress is a significant risk factor for the onset of mood disorders such as depression during adulthood. Impairments in cognitive flexibility mediated by prefrontal cortex (PFC) dysfunction are increasingly recognized as important etiological and pathological factors in the development of depression. Our previous study demonstrated that social defeat stress during early adolescence produced delayed deficits in cognitive flexibility in adult mice. The potential molecular mechanisms underlying these long-term consequences remain unclear...
2016: Frontiers in Molecular Neuroscience
Peter R Bieck, Mark Leibowitz, D Richard Lachno, Edouard Ledent, Robert Padich, Stan Jhee
To assess the primary metabolite of norepinephrine, 3,4-dihydroxyphenylglycol (DHPG), as a sensitive biomarker for norepinephrine transporter (NET) function and the relationship of DHPG measured peripherally and centrally, NET was antagonized with 80 mg/d atomoxetine for 18 days. Twelve healthy subjects were treated with atomoxetine in an open-label, multiple-dose exploratory study. Plasma atomoxetine reached steady state by day 6, and the pharmacokinetic results demonstrated availability of atomoxetine to the central nervous system...
October 15, 2016: Journal of Clinical Psychopharmacology
Kei Ando, Shiro Imagama, Zenya Ito, Kazuyoshi Kobayashi, Tetsuro Hida, Hiroaki Nakashima, Kenyu Ito, Mikito Tsushima, Yoshimoto Ishikawa, Akiyuki Matsumoto, Koji Nishida, Yoshihiro Nishida, Naoki Ishiguro
STUDY DESIGN: Self-assembling peptide gel (SPG-178) provides new evidence for the role of a scaffold for treatment of the spinal cord through induction of neuroprotective factors. OBJECTIVE: To verify the reproducibility of SPG-178 as scaffold after spinal cord injury, we examine the characteristics of SPG-178 and protective effect on neural cells in vitro and in vivo. SUMMARY OF BACKGROUND DATA: The central nervous system extracellular matrix may play a role in maintenance of the neuronal network by inhibiting axonal growth and suppressing formation of additional inadequate synapses...
October 15, 2016: Spine
Zhongyan Hua, Xiao Gu, Yudi Dong, Fei Tan, Zhihui Liu, Carol J Thiele, Zhijie Li
Brain-derived neurotrophic factor (BDNF) and its tyrosine kinase receptor TrkB have been reported to be associated with poor prognosis in neuroblastoma (NB) patients. Our previous studies indicated that BDNF activation of TrkB induces chemo-resistance through activation of phosphoinositide-3-kinase (PI3K)/Akt pathway. In this study, we investigated the role of BDNF/TrkB on metastasis in NB. A tetracycline-regulated TrkB-expressing NB cell line (TB3) was used. Scratch wound healing assay, Boyden chamber migration, and invasion assays were performed to study the migration and invasion of TB3 cells...
October 17, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Bo Jiang, Lin Gao, Dawei Lei, Jiannan Liu, Zhengbo Shao, Xinrong Zhou, Renke Li, Donglai Wu, Fei Xue, Yuanmao Zhu, Huiping Yuan
The aims of the present study were to investigate the effect of E50K optineurin (OPTN) mutation on RGC‑5 cells and to define the role of microRNA‑9 (miR‑9) in this system. Transfected RGC‑5 cells were used to evaluate the effects of E50K OPTN on the expression of miR‑9 and subsequent disruption of RGC‑5 cell apoptosis was analyzed using western blotting. The results showed that the expression of E50K OPTN was associated with a marked reduction in the levels of miR‑9 in the E50K OPTN‑transfected RGC‑5 cells...
October 6, 2016: Molecular Medicine Reports
Jie Yang, Xianying Wang, Sha Liu, Gai Xue
OBJECTIVE: To investigate whether promotion of neuronal differentiation of human umbilical cord mesenchymal stem cells (HUMSCs) by progesterone (PROG) involves changes in brain-derived neurotrophic factor (BDNF) levels. METHODS: We used rat brain tissue extracts to mimic the brain microenvironment. Quantitative sandwich enzyme-linked immunosorbent assay was performed to measure levels of BDNF in cultured medium with or without PROG. RESULTS: Progesterone increased levels of BDNF in HUMSCs...
October 17, 2016: Neurological Research
Y-B Yu, D-Y Zhao, Q-Q Qi, X Long, X Li, F-X Chen, X-L Zuo
BACKGROUND: Brain-derived neurotrophic factor (BDNF) may play a vital role in the homeostatic regulation of intestinal barrier integrity. We aimed to investigate the physiological role of BDNF in maintaining the intestinal epithelial barrier using postinflammatory irritable bowel syndrome (PI-IBS) mice and explore the underlying molecular mechanisms using intestinal epithelial cells in vitro. METHODS: Postinflammatory-IBS mice were induced by intrarectal administration of trinitrobenzene sulfonic acid and allowed to recover for 28 days...
October 17, 2016: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
Beatrice Vignoli, Giulia Battistini, Riccardo Melani, Robert Blum, Spartaco Santi, Nicoletta Berardi, Marco Canossa
Glial cells respond to neuronal activation and release neuroactive molecules (termed "gliotransmitters") that can affect synaptic activity and modulate plasticity. In this study, we used molecular genetic tools, ultra-structural microscopy, and electrophysiology to assess the role of brain-derived neurotrophic factor (BDNF) on cortical gliotransmission in vivo. We find that glial cells recycle BDNF that was previously secreted by neurons as pro-neurotrophin following long-term potentiation (LTP)-inducing electrical stimulation...
October 12, 2016: Neuron
Fernanda Peres da Silveira, Carla Basso, Wagner Raupp, Morgana Dalpiaz, Karine Bertoldi, Ionara Rodrigues Siqueira, Pedro Dal Lago, Maristela Padilha de Souza, Viviane Rostirola Elsner
Our aim was to compare the basal levels of plasma brain-derived neurotrophic factor (BDNF) and global histone H4 acetylation in peripheral blood mononuclear cells (PBMCs) of healthy amateur runners (EXE group) with sedentary individuals (SED group) as well as to investigate the acute effect of a running race on these markers in the EXE group. Five days before the race, all participants were submitted to a basal blood collection. On the race day, two blood samples were collected in the EXE group before the running started and immediately at the end...
October 14, 2016: Journal of Physiological Sciences: JPS
Krisztina Marosi, Sang Woo Kim, Keelin Moehl, Morten Scheibye-Knudsen, Aiwu Cheng, Roy Cutler, Simonetta Camandola, Mark P Mattson
During fasting and vigorous exercise, a shift of brain cell energy substrate utilization from glucose to the ketone 3-hydroxybutyrate (3OHB) occurs. Studies have shown that 3OHB can protect neurons against excitotoxicity and oxidative stress, but the underlying mechanisms are unclear. Neurons maintained in the presence of 3OHB exhibited increased oxygen consumption and ATP production, and an elevated NAD+/NADH ratio. We found that 3OHB metabolism increases mitochondrial respiration which drives changes in expression of brain derived neurotrophic factor (BDNF) in cultured cerebral cortical neurons...
October 14, 2016: Journal of Neurochemistry
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