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https://www.readbyqxmd.com/read/28746076/safety-and-efficacy-of-neublastin-in-painful-lumbosacral-radiculopathy-a-randomized-double-blinded-placebo-controlled-phase-2-trial-using-bayesian-adaptive-design-the-sprint-trial
#1
Miroslav Backonja, Leslie Williams, Xiaopeng Miao, Nathaniel Katz, Crystal Chen
Neublastin (BG00010) is a first-in-class, glial cell-derived neurotrophic factor shown in preclinical studies and an early clinical trial to have potential for the treatment of neuropathic pain. SPRINT was a phase 2, multicenter, double-blinded, placebo-controlled study to evaluate efficacy/safety of 5 neublastin doses (50, 150, 400, 800, and 1200 μg/kg) administered as an intravenous injection 3 times/week for 1 week in patients with chronic painful lumbosacral radiculopathy, utilizing Bayesian response-adaptive study design...
June 21, 2017: Pain
https://www.readbyqxmd.com/read/28733972/expression-and-function-of-the-metabotropic-purinergic-p2y-receptor-family-in-experimental-seizure-models-and-patients-with-drug-refractory-epilepsy
#2
Mariana Alves, Rosa Gomez-Villafuertes, Norman Delanty, Michael A Farrell, Donncha F O'Brien, Maria Teresa Miras-Portugal, Miguel Diaz Hernandez, David C Henshall, Tobias Engel
OBJECTIVE: ATP is released into the extracellular space during pathologic processes including increased neuronal firing. Once released, ATP acts on P2 receptors including ionotropic P2X and metabotropic P2Y receptors, resulting in changes to glial function and neuronal network excitability. Evidence suggests an involvement of P2Y receptors in the pathogenesis of epilepsy, but there has been no systematic effort to characterize the expression and function of the P2Y receptor family during seizures and in experimental and human epilepsy...
July 21, 2017: Epilepsia
https://www.readbyqxmd.com/read/28733667/rtn1-and-rtn3-protein-are-differentially-associated-with-senile-plaques-in-alzheimer-s-brains
#3
Qi Shi, Yingying Ge, Wanxia He, Xiangyou Hu, Riqiang Yan
Reticulon proteins (RTNs), consisting of RTN1 to RTN4, were previously shown to interact with BACE1 by negatively modulating its secretase activity. In RTN3-null mice, RTN1 expression was slightly elevated. To understand the in vivo role of RTN1, we generated RTN1-null mice and compared the effects of RTN1 and RTN3 on BACE1 modulation. We show that RTN1 is mostly expressed by neurons and not by glial cells under normal conditions, similar to the expression of RTN3. However, RTN1 is more localized in dendrites and is an excellent marker for dendrites of Purkinje cells, while RTN3 expression is less evident in dendrites...
July 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28730967/microglia-and-astrocytes-in-alzheimer-s-disease-implications-for-therapy
#4
Marc Fakhoury
Alzheimer's disease (AD) is a complex neurodegenerative disorder characterized by the progressive loss of neurons, which typically leads to severe impairments in cognitive functions including memory and learning. Key pathological features of this disease include the deposition of highly insoluble amyloid β peptide and the formation of neurofibrillary tangles (NFTs) in the brain. Over the past few years, mounting evidence has implicated sustained glial-mediated inflammation as a major contributor of the neurodegenerative processes and cognitive deficits observed in AD...
July 19, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28711628/enteric-glia-regulate-gastrointestinal-motility-but-are-not-required-for-maintenance-of-the-epithelium-in-mice
#5
Meenakshi Rao, Daniella Rastelli, Lauren Dong, Sophia Chiu, Wanda Setlik, Michael D Gershon, Gabriel Corfas
BACKGROUND & AIMS: When the glial fibrillary acidic protein (GFAP) promoter is used to express cellular toxins that eliminate glia in mice, intestinal epithelial permeability and proliferation increase; this led to the concept that glia are required for maintenance of the gastrointestinal epithelium. Many enteric glia, however, particularly in the mucosa, do not express GFAP. In contrast, virtually all enteric glia express proteolipid protein 1 (PLP1). We investigated whether elimination of PLP1-expressing cells compromises epithelial maintenance or gastrointestinal motility...
July 12, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28707354/additive-neurogenesis-supported-by-multiple-stem-cell-populations-mediates-adult-spinal-cord-development-a-spatio-temporal-statistical-mapping-analysis-in-a-teleost-model-of-indeterminate-growth
#6
Ruxandra F Sîrbulescu, Iulian Ilieş, Annette Meyer, Günther K H Zupanc
The knifefish Apteronotus leptorhynchus exhibits indeterminate growth throughout adulthood. This phenomenon extends to the spinal cord, presumably through the continuous addition of new neurons and glial cells. However, little is known about the developmental dynamics of cells added during adult growth. The present work characterizes the structural and functional development of the adult spinal cord in this model organism through a comprehensive quantitative analysis of the spatial and temporal dynamics of new cells at various developmental stages...
July 13, 2017: Developmental Neurobiology
https://www.readbyqxmd.com/read/28698967/endogenous-expression-of-odn-related-peptides-in-astrocytes-contributes-to-cell-protection-against-oxidative-stress-astrocyte-neuron-crosstalk-relevance-for-neuronal-survival
#7
Ikram Ghouili, Seyma Bahdoudi, Fabrice Morin, Fatma Amri, Yosra Hamdi, Pierre Michael Coly, Marie-Laure Walet-Balieu, Jérôme Leprince, Sami Zekri, Hubert Vaudry, David Vaudry, Hélène Castel, Mohamed Amri, Marie-Christine Tonon, Olfa Masmoudi-Kouki
Astroglial cells are important actors in the defense of brain against oxidative stress injuries. Glial cells synthesize and release the octadecaneuropeptide ODN, a diazepam-binding inhibitor (DBI)-related peptide, which acts through its metabotropic receptor to protect neurons and astrocytes from oxidative stress-induced apoptosis. The purpose of the present study is to examine the contribution of the endogenous ODN in the protection of astrocytes and neurons from moderate oxidative stress. The administration of H2O2 (50 μM, 6 h) induced a moderate oxidative stress in cultured astrocytes, i...
July 11, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28695372/increased-expression-of-translocator-protein-tspo-marks-pro-inflammatory-microglia-but-does-not-predict-neurodegeneration
#8
Lien Beckers, Dieter Ory, Ivana Geric, Lieven Declercq, Michel Koole, Michael Kassiou, Guy Bormans, Myriam Baes
PURPOSE: Activation of the innate immune system plays a significant role in pathologies of the central nervous system (CNS). In order to follow disease progression and evaluate effectiveness of potential treatments involved in neuroinflammation, it is important to track neuroinflammatory markers in vivo longitudinally. The translocator protein (TSPO) is used as a target to image neuroinflammation as its expression is upregulated in reactive glial cells during CNS pathologies. However, it remains unclear in which microglial phenotypes TSPO levels are upregulated, as microglia can display a plethora of activation states that can be protective or detrimental to the CNS...
July 10, 2017: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
https://www.readbyqxmd.com/read/28694468/interactome-and-reciprocal-activation-of-pathways-in-topical-mesenchymal-stem-cells-and-the-recipient-cerebral-cortex-following-traumatic-brain-injury
#9
Ping K Lam, Kevin K W Wang, Anthony W I Lo, Cindy S W Tong, Don W C Ching, Kenneth Wong, Zhihui Yang, Themis Kong, Kin K Y Lo, Richard K W Choy, Paul B S Lai, George K C Wong, Wai S Poon
In this study, GFP-MSCs were topically applied to the surface of cerebral cortex within 1 hour of experimental TBI. No treatment was given to the control group. Three days after topical application, the MSCs homed to the injured parenchyma and improved the neurological function. Topical MSCs triggered earlier astrocytosis and reactive microglia. TBI penumbra and hippocampus had higher cellular proliferation. Apoptosis was suppressed at hippocampus at 1 week and reduced neuronal damaged was found in the penumbral at day 14 apoptosis...
July 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28694214/visualization-of-migration-of-human-cortical-neurons-generated-from-induced-pluripotent-stem-cells
#10
Yohei Bamba, Yonehiro Kanemura, Hideyuki Okano, Mami Yamasaki
BACKGROUND: Neuronal migration is considered a key process in human brain development. However, direct observation of migrating human cortical neurons in the fetal brain is accompanied by ethical concerns and is a major obstacle in investigating human cortical neuronal migration. NEW METHOD: We established a novel system that enables direct visualization of migrating cortical neurons generated from human induced pluripotent stem cells (hiPSCs). RESULTS: We observed the migration of cortical neurons generated from hiPSCs derived from a control and from a patient with lissencephaly...
July 8, 2017: Journal of Neuroscience Methods
https://www.readbyqxmd.com/read/28689143/glial-cell-line-derived-neurotrophic-factor-gdnf-serum-level-in-women-with-schizophrenia-and-depression-correlation-with-clinical-and-metabolic-parameters
#11
Maria Skibinska, Pawel Kapelski, Joanna Pawlak, Aleksandra Rajewska-Rager, Monika Dmitrzak-Weglarz, Aleksandra Szczepankiewicz, Piotr Czerski, Joanna Twarowska-Hauser
AIM: Neurotrophic factors have been implicated in neuropsychiatric disorders, including schizophrenia and depression. Glial Cell Line-Derived Neurotrophic Factor (GDNF) promotes development, differentiation, and protection of dopaminergic, serotonergic, GABAergic and noradrenergic neurons as well as glial cells in different brain regions. This study examined serum levels of GDNF in schizophrenia and depression and its correlation with metabolic parameters during 8 weeks of treatment. METHODS: Serum GDNF level, fasting serum glucose and lipid profile were measured at baseline and week 8 in 133 women: 55 with schizophrenia, 30 with a first episode depression and 48 healthy controls...
July 6, 2017: Psychiatry Research
https://www.readbyqxmd.com/read/28687401/pathophysiological-role-of-prostaglandin-e2-induced-up-regulation-of-the-ep2-receptor-in-motor-neuron-like-nsc-34-cells-and-lumbar-motor-neurons-in-als-model-mice
#12
Yasuhiro Kosuge, Hiroko Miyagishi, Yuki Yoneoka, Keiko Yoneda, Hiroshi Namgo, Kumiko Ishige, Yoshihisa Ito
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by selective degeneration of motor neurons. The primary triggers for motor neuronal death are still unknown, but inflammation is considered to be an important factor contributing to the pathophysiology of ALS both clinically and in ALS models. Prostaglandin E2 (PGE2) and its corresponding four E-prostanoid receptors play a pivotal role in the degeneration of motor neurons in human and transgenic models of ALS. It has also been shown that PGE2-EP2 signaling in glial cells (astrocytes or microglia) promotes motor neuronal death in G93A mice...
July 4, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28684912/the-effects-of-grafted-mesenchymal-stem-cells-labeled-with-iron-oxide-or-cobalt-zinc-iron-nanoparticles-on-the-biological-macromolecules-of-rat-brain-tissue-extracts
#13
Bozena Novotna, Vit Herynek, Pavel Rossner, Karolina Turnovcova, Pavla Jendelova
INTRODUCTION: Rat mesenchymal stem cells (rMSCs) labeled with 1) poly-l-lysine-coated superparamagnetic iron oxide nanoparticles or 2) silica-coated cobalt-zinc-iron nanoparticles were implanted into the left brain hemisphere of rats, to assess their effects on the levels of oxidative damage to biological macromolecules in brain tissue. METHODS: Controls were implanted with unlabeled rMSCs. Animals were sacrificed 24 hours or 4 weeks after the treatment, and the implantation site along with the surrounding tissue was isolated from the brain...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28680400/a-novel-small-molecule-gdnf-receptor-ret-agonist-bt13-promotes-neurite-growth-from-sensory-neurons-in-vitro-and-attenuates-experimental-neuropathy-in-the-rat
#14
Yulia A Sidorova, Maxim M Bespalov, Agnes W Wong, Oleg Kambur, Viljami Jokinen, Tuomas O Lilius, Ilida Suleymanova, Gunnar Karelson, Pekka V Rauhala, Mati Karelson, Peregrine B Osborne, Janet R Keast, Eija A Kalso, Mart Saarma
Neuropathic pain caused by nerve damage is a common and severe class of chronic pain. Disease-modifying clinical therapies are needed as current treatments typically provide only symptomatic relief; show varying clinical efficacy; and most have significant adverse effects. One approach is targeting either neurotrophic factors or their receptors that normalize sensory neuron function and stimulate regeneration after nerve damage. Two candidate targets are glial cell line-derived neurotrophic factor (GDNF) and artemin (ARTN), as these GDNF family ligands (GFLs) show efficacy in animal models of neuropathic pain (Boucher et al...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28676971/an-in-vitro-study-ascertaining-the-role-of-h2o2-and-glucose-oxidase-in-modulation-of-antioxidant-potential-and-cancer-cell-survival-mechanisms-in-glioblastoma-u-87-mg-cells
#15
Ravi P Cholia, Sanju Kumari, Saurabh Kumar, Manpreet Kaur, Manbir Kaur, Raj Kumar, Monisha Dhiman, Anil K Mantha
Glial cells protect themselves from the elevated reactive oxygen species (ROS) via developing unusual mechanisms to maintain the genomic stability, and reprogramming of the cellular antioxidant system to cope with the adverse effects. In the present study non-cytotoxic dose of oxidants, H2O2 (100 μM) and GO (10 μU/ml) was used to induce moderate oxidative stress via generating ROS in human glioblastoma cell line U-87 MG cells, which showed a marked increase in the antioxidant capacity as studied by measuring the modulation in expression levels and activities of superoxide dismutase (SOD1 and SOD2) and catalase (CAT) enzymes, and the GSH content...
July 5, 2017: Metabolic Brain Disease
https://www.readbyqxmd.com/read/28662512/ru486-reverses-emotional-disorders-by-influencing-astrocytes-and-endoplasmic-reticulum-stress-in-chronic-restraint-stress-challenged-rats
#16
Liru Dong, Songjun Wang, Yingmin Li, Ziqin Zhao, Yiwen Shen, Li Liu, Guangming Xu, Chunling Ma, Shujin Li, Xiaojing Zhang, Bin Cong
AIMS: To investigate the effect of RU486 (mifepristone) on emotional disorders in chronic restraint stress-induced rats and to explore the mechanisms of that phenomenon. METHODS: For this purpose, 80 healthy male Sprague Dawley rats were randomly divided into four groups: the normal group (Con group, The Con group members received no treatment, eating and drinking freely), the chronic restraint stress group (CRS group, normal Sprague Dawley rats treated with chronic restraint stress, 6 h/day for 21days), the propylene glycol group (CRS+propylene glycol) and the RU486 group (CRS+RU486)...
June 29, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28655291/naturally-acquired-canine-herpesvirus-associated-meningoencephalitis
#17
Mason C Jager, Erica A Sloma, Morgan Shelton, Andrew D Miller
Canid alphaherpesvirus 1 (CHV) causes morbidity and mortality in susceptible puppies. While the neuropathology of experimentally infected puppies has been detailed, characterization of naturally acquired infections is limited. The aim of this study was to describe the histologic, immunohistochemical, and in situ hybridization features of CHV encephalitis in the dog. Six female and 11 male puppies ranging in age from stillborn to 57 days old were included. Histologically, lesions included multifocal glial nodules (16/17, 94%), meningeal infiltrates (15/17, 88%), and cerebellar cortical necrosis (6/9, 67%); however, robust inflammation was not a significant feature in any of the cases...
January 1, 2017: Veterinary Pathology
https://www.readbyqxmd.com/read/28650574/injection-of-microporous-annealing-particle-map-hydrogels-in-the-stroke-cavity-reduces-gliosis-and-inflammation-and-promotes-npc-migration-to-the-lesion
#18
Lina R Nih, Elias Sideris, S Thomas Carmichael, Tatiana Segura
With the number of deaths due to stroke decreasing, more individuals are forced to live with crippling disability resulting from the stroke. To date, no therapeutics exist after the first 4.5 h after the stroke onset, aside from rest and physical therapy. Following stroke, a large influx of astrocytes and microglia releasing proinflammatory cytokines leads to dramatic inflammation and glial scar formation, affecting brain tissue's ability to repair itself. Pathological conditions, such as a stroke, trigger neural progenitor cells (NPCs) proliferation and migration toward the damaged site...
June 26, 2017: Advanced Materials
https://www.readbyqxmd.com/read/28646353/creb1-regulates-glucose-transport-of-glioma-cell-line-u87-by-targeting-glut1
#19
Jiaying Chen, Can Zhang, Yang Mi, Fuxue Chen, Dongshu Du
Glioma is stemmed from the glial cells in the brain, which is accounted for about 45% of all intracranial tumors. The characteristic of glioma is invasive growth, as well as there is no obvious boundary between normal brain tissue and glioma tissue, so it is difficult to resect completely with worst prognosis. The metabolism of glioma is following the Warburg effect. Previous researches have shown that GLUT1, as a glucose transporter carrier, affected the Warburg effect, but the molecular mechanism is not very clear...
June 23, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28645787/striatal-hypodopamine-phenotypes-found-in-transgenic-mice-that-overexpress-glial-cell-line-derived-neurotrophic-factor
#20
Hidekazu Sotoyama, Yuriko Iwakura, Kanako Oda, Toshikuni Sasaoka, Nobuyuki Takei, Akiyoshi Kakita, Hideki Enomoto, Hiroyuki Nawa
Glial cell line-derived neurotrophic factor (GDNF) positively regulates the development and maintenance of in vitro dopaminergic neurons. However, the in vivo influences of GDNF signals on the brain dopamine system are controversial and not fully defined. To address this question, we analyzed dopaminergic phenotypes of the transgenic mice that overexpress GDNF under the control of the glial Gfap promoter. Compared with wild-type, the GDNF transgenic mice contained higher levels of GDNF protein and phosphorylated RET receptors in the brain...
June 21, 2017: Neuroscience Letters
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