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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
Ke-Wei Tian, Fan Zhang, Hong Jiang, Beibei Wang, Shu Han
Multiple sclerosis (MS) is a chronic neurological disorder that affects the central nervous system (CNS), and results in CNS inflammation and damage to myelin. In this study, we examined the possible synergistic effects of C16, angiopoietin-1 (Ang-1) and regeneration gene protein 2 (Reg-2) in alleviating inflammation in an acute experimental autoimmune encephalomyelitis (EAE) model. We employed multiple histological, morphological and iconographic assays to examine the effect of those drugs on disease onset, clinical scores and behavioral deficits...
October 19, 2016: Journal of Anatomy
Rosalia Pellitteri, Roberta Bonfanti, Michela Spatuzza, Maria Teresa Cambria, Mariacristina Ferrara, Giuseppina Raciti, Agata Campisi
Herein, we assessed in a particular glial cell type, called olfactory ensheathing cells (OECs), the effect of some growth factors (GFs) on tissue transglutaminase (TG2) overexpression induced by amyloid-beta (Aβ) with native full-length peptide 1-42 or by fragments, 25-35 or 35-25, as control. Previously, we demonstrated that TG2 overexpression induced by some stressors was down-regulated by GFs exposure in OECs. To monitor cell viability, an MTT test was used, while TG2 expression was examined using immunocytochemical and Western blot analysis...
October 18, 2016: Molecular Neurobiology
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
Rachelle T Hassarati, L John R Foster, Rylie A Green
The recent success of olfactory ensheathing cell (OEC) assisted regeneration of injured spinal cord has seen a rising interest in the use of these cells in tissue-engineered systems. Previously shown to support neural cell growth through glial scar tissue, OECs have the potential to assist neural network formation in living electrode systems to produce superior neuroprosthetic electrode surfaces. The following study sought to understand the influence of biphasic electrical stimulation (ES), inherent to bionic devices, on cell survival and function, with respect to conventional metallic and developmental conductive hydrogel (CH) coated electrodes...
2016: Frontiers in 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
Ari L Mendell, Carolyn E Creighton, Bettina E Kalisch, Neil J MacLusky
Low free testosterone levels in men are associated with age-related cognitive decline and increased risk for neurotoxicity, resulting in disease. The mechanisms underlying these observations remain poorly defined. While rapid, androgen receptor-dependent activation of extracellular signal-regulated kinase (ERK) has been postulated as a neurotrophic and neuroprotective mechanism, actions of testosterone metabolites such as 5α-androstane-3α,17β-diol (3α-diol) may also be involved. We investigated the influence of 3α-diol on the induction of ERK phosphorylation in SH-SY5Y human female neuroblastoma cells and primary cortical neurons from male and female mice...
October 18, 2016: Endocrinology
Yuan-Yuan Wang, Jun-Mian Tian, Cheng-Chen Zhang, Bo Luo, Jin-Ming Gao
Two picrotoxane sesquiterpene lactone glycosides, nepalactones A (1) and B (2), and one new coumarin, nepalarin (3), were isolated from the root barks of the poisonous plant Coriarianepalensis. Their structures were elucidated via HRESIMS and 1D and 2D NMR spectroscopic analyses, and further verified via transformation methods. In addition, compounds 1-3 and five semisynthetic congeners (1a-e) were assayed for the activity to induce neurite outgrowth in rat pheochromocytoma (PC12) cells. As a result, nepalactone A derivative 1c and nepalarin (3) significantly enhanced nerve growth factor (NGF)-mediated neurite outgrowth in PC12 cells...
October 12, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
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
Natalia A Stefanova, Natalia A Muraleva, Kseniya Yi Maksimova, Ekaterina A Rudnitskaya, Elena Kiseleva, Darya V Telegina, Nataliya G Kolosova
Mitochondrial aberrations are observed in human Alzheimer's disease (AD) and in medical conditions that increase the risk of this disorder, suggesting that mitochondrial dysfunction may contribute to pathophysiology of AD. Here, using OXYS rats that simulate key characteristics of sporadic AD, we set out to determine the role of mitochondria in the pathophysiology of this disorder. OXYS rats were treated with a mitochondria-targeted antioxidant SkQ1 from age 12 to 18 months, that is, during active progression of AD-like pathology in these animals...
October 6, 2016: Aging
Ying Li Gu, Guan Qun Gao, Ning Ma, Lin Lin Ye, Li Wei Zhang, Xu Gao, Zhuo Bo Zhang
The aim of the present study was to investigate whether ciliary neurotrophic factor (CNTF) plays its neuroprotective role following hypoxic injury through the activation of signal transducer and activator of transcription 3 (STAT3) signaling. Firstly, to determine whether CNTF exerts its effects via STAT3 following hypoxic injury, cultured neurons from the cerebral cortex of mice were prepared and a neuronal model of hypoxia was then established. The neurons exposed to hypoxia were then pre-treated with CNTF and transfected with small interference RNA (siRNA) targeting STAT3 (STAT3 siRNA) using polybrene, or with STAT3Tyr705 mutant or STAT3Ser727 mutant using an electroporation system...
October 13, 2016: International Journal of Molecular 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
Cyrus Vahdatpour, Adam H Dyer, Daniela Tropea
Insulin-Like Growth Factor 1 (IGF-1) is a neurotrophic polypeptide with crucial roles to play in Central Nervous System (CNS) growth, development and maturation. Following interrogation of the neurobiology underlying several neurodevelopmental disorders and Autism Spectrum Disorders (ASD), both recombinant IGF-1 (mecasermin) and related derivatives, such as (1-3)IGF-1, have emerged as potential therapeutic approaches. Clinical pilot studies and early reports have supported the safety/preliminary efficacy of IGF-1 and related compounds in the treatment of Rett Syndrome, with evidence mounting for its use in Phelan McDermid Syndrome and Fragile X Syndrome...
2016: Frontiers in Neuroscience
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