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Kazuo Kunisawa, Takeshi Shimizu, Itaru Kushima, Branko Aleksic, Daisuke Mori, Yasuyuki Osanai, Kenta Kobayashi, Anna M Taylor, Manzoor A Bhat, Akiko Hayashi, Hiroko Baba, Norio Ozaki, Kazuhiro Ikenaka
Myelinated axons segregate the axonal membrane into four defined regions: the node of Ranvier, paranode, juxtaparanode and internode. The paranodal junction consists of specific component proteins, such as neurofascin155 (NF155) on the glial side, and Caspr and Contactin on the axonal side. Although paranodal junctions are thought to play crucial roles in rapid saltatory conduction and nodal assembly, the role of their interaction with neurons is not fully understood. In a previous study, conditional NF155 knockout in oligodendrocytes led to disorganization of the paranodal junctions...
July 19, 2018: Journal of Neurochemistry
Eriko Shimada, Fasih M Ahsan, Mahta Nili, Dian Huang, Sean Atamdede, Tara TeSlaa, Dana Case, Xiang Yu, Brian D Gregory, Benjamin J Perrin, Carla M Koehler, Michael A Teitell
Polynucleotide phosphorylase (PNPase) is an essential mitochondria-localized exoribonuclease implicated in multiple biological processes and human disorders. To reveal role(s) for PNPase in mitochondria, we established PNPase knockout (PKO) systems by first shifting culture conditions to enable cell growth with defective respiration. Interestingly, PKO established in mouse embryonic fibroblasts (MEFs) resulted in the loss of mitochondrial DNA (mtDNA). The transcriptional profile of PKO cells was similar to rho0 mtDNA deleted cells, with perturbations in cholesterol (FDR = 6...
2018: PloS One
Masahiro Sakita, Shinichiro Murakami, Hidemi Fujino, Satoshi Hayashi, Kazuyoshi Kameyama, Takafumi Saito, Shuzo Kumagai
The aim of this study was to determine whether aerobic exercise (AE) in old age contributes to improving the morphologies of myelinated fibers (MFs) in peripheral nerves as well as capillaries. Furthermore, we investigated whether such processes are associated with complementary activity of brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) in the circulating blood and peripheral nerve tissue. Fourteen male Wistar rats (age: 95 weeks) were randomly divided into moderate AE (n=8) and sedentary (SED; n=6) groups...
July 19, 2018: Journal of Applied Physiology
Yanteng Zhao, Qiang Zhang, Lei Zhao, Li Gan, Li Yi, Yanan Zhao, Jingling Xue, Lihua Luo, Qiaoyue Du, Rongxin Geng, Zhihong Sun, Nadia Benkirane-Jessel, Pu Chen, Yinping Li, Yun Chen
Multichannel nerve guide conduits (MCNGCs) have been widely studied and exhibited outstanding nerve repair function. However, the effect of the geometric structure of MCNGCs on the nerve repair function was still not clear. Herein, we postulated that MCNGCs with different inner surface area-to-volume ratios (ISA/V) of the channels inside the nerve guide conduits (NGCs) would show different nerve repair functions. Therefore, in current work, we constructed a series of hydroxyethyl cellulose/soy protein sponge-based nerve conduit (HSSN) with low, medium, and high ISA/V from hydroxyethyl cellulose (HEC)/soy protein isolate (SPI) composite sponges, which were abbreviated as HSSN-L, HSSN-M and HSSN-H, respectively...
November 30, 2017: ACS Omega
Quangang Xu, Wenjuan Du, Huanfen Zhou, Xin Zhang, Hongjuan Liu, Honglu Song, Xueqiong Wang, Shihui Wei
OBJECTIVE: Paraneoplastic optic neuropathy (PON) is relatively uncommon, and the visual outcomes and prognosis of this disease have not been well documented. The aim of this study was to investigate the clinical features and prognosis of antibody-mediated PON. METHODS: Clinical data were retrospectively collected from hospitalised patients diagnosed with PON at the Neuro-Ophthalmology Department at the Chinese People's Liberation Army General Hospital from January 2015 to June 2017...
July 18, 2018: British Journal of Ophthalmology
Loïc Dayon, Antonio Núñez Galindo, Jérôme Wojcik, Ornella Cominetti, John Corthésy, Aikaterini Oikonomidi, Hugues Henry, Martin Kussmann, Eugenia Migliavacca, India Severin, Gene L Bowman, Julius Popp
BACKGROUND: Altered proteome profiles have been reported in both postmortem brain tissues and body fluids of subjects with Alzheimer disease (AD), but their broad relationships with AD pathology, amyloid pathology, and tau-related neurodegeneration have not yet been fully explored. Using a robust automated MS-based proteomic biomarker discovery workflow, we measured cerebrospinal fluid (CSF) proteomes to explore their association with well-established markers of core AD pathology. METHODS: Cross-sectional analysis was performed on CSF collected from 120 older community-dwelling adults with normal (n = 48) or impaired cognition (n = 72)...
July 18, 2018: Alzheimer's Research & Therapy
Haiyan Pan, Yuanlin Ding, Ning Yan, Yaxin Nie, Mei Li, Linyan Tong
Type 1 diabetes (T1DM) affects approximately 1 in 500 children. Diabetic peripheral neuropathy (DPN) is the most common form of peripheral neuropathy in diabetes and is a significant risk factor for serious pathological change. It is difficult and costly to treat DPN and although there have been several pivotal trials. The development of new drugs to treat DPN remains a high priority. Trehalose is a naturally occurring disaccharide, which is indicated to prevent maternal type 1 diabetes-induced neural tube defects...
September 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Bruno Stankoff, Emilie Poirion, Matteo Tonietto, Benedetta Bodini
The biological mechanisms driving disability worsening in multiple sclerosis (MS) are only partly understood.. Monitoring changes in lesion load on MRI has a limited predictive value on the development of clinical disability, and there is an essential need for novel imaging markers specific for the main candidate mechanisms underlying neurodegeneration which include failing myelin repair, innate immune cell activation and grey matter neuronal damage. Positron Emission Tomography (PET) is an imaging technology based on the injection of radiotracers directed against specific molecular targets and has recently allowed the selective quantification in-vivo of the key biological mechanisms relevant to MS pathophysiology...
July 18, 2018: Brain Pathology
Simon Hametner, Assunta Dal Bianco, Siegfried Trattnig, Hans Lassmann
Iron accumulates with age in the normal human brain. This process is altered at several levels in the brain of multiple sclerosis (MS) patients. Since iron is mainly stored in oligodendrocytes and myelin in the normal brain, its liberation in demyelinating lesions may amplify tissue damage in demyelinating lesions and its uptake in macrophages and microglia may help to more precisely define activity stages of the lesions. In addition, glia cells change their iron import, export and storage properties in MS lesions, which is reflected by alterations in the expression of iron transport molecules...
July 18, 2018: Brain Pathology
Nathalie Laflamme, Giulia Cisbani, Paul Préfontaine, Younes Srour, Jordan Bernier, Marie-Kim St-Pierre, Marie-Ève Tremblay, Serge Rivest
A pathological hallmark of multiple sclerosis (MS) is myelin loss in brain white matter accompanied by compromised remyelination. Demyelinated lesions are deeply associated with oligodendrocyte apoptosis and a robust inflammatory response. Although various studies point towards a noxious role of inflammation in MS, others emphasize a positive role for the innate immune cells in disease progression. A cytokine well-known to stimulate cell survival, proliferation and differentiation of myeloid cells, macrophage colony-stimulating factor (mCSF), was administered to mice during a 5 week-long cuprizone diet...
2018: Frontiers in Cellular Neuroscience
Martial Caillaud, Benjamin Chantemargue, Laurence Richard, Laetitia Vignaud, Frédéric Favreau, Pierre-Antoine Faye, Philippe Vignoles, Franck Sturtz, Patrick Trouillas, Jean-Michel Vallat, Alexis Desmoulière, Fabrice Billet
Traumatic injuries to peripheral nerves are frequent, however, specific pharmacological treatments are currently lacking. Curcumin has antioxidant, anti-inflammatory and neuroprotective properties but high oral doses are required for therapeutic use, particularly due to its low bioavailability. The aim of the present study was to investigate the effects of local and continuous treatment using low curcumin doses on functional recovery and nerve regeneration after rat sciatic nerve crush (SNC). Curcumin was administered by osmotic pumps with a catheter delivering the drug at the injury site (0...
July 3, 2018: Neuropharmacology
J Lebenberg, J-F Mangin, B Thirion, C Poupon, L Hertz-Pannier, F Leroy, P Adibpour, G Dehaene-Lambertz, J Dubois
While the main neural networks are in place at term birth, intense changes in cortical microstructure occur during early infancy with the development of dendritic arborization, synaptogenesis and fiber myelination. These maturational processes are thought to relate to behavioral acquisitions and the development of cognitive abilities. Nevertheless, in vivo investigations of such relationships are still lacking in healthy infants. To bridge this gap, we aimed to study the cortical maturation using non-invasive Magnetic Resonance Imaging, over a largely unexplored period (1-5 post-natal months)...
July 11, 2018: NeuroImage
Kana Yokota, Kentaro Sano, Yuka Murofushi, Daisuke Yoshimaru, Jun-Ichi Takanashi
MRI of a female patient with xeroderma pigmentosum group A (XP-A) showed progressive cerebral atrophy, but no disease-specific lesion. MR spectroscopy with short TE sequences in the bilateral white matter revealed decreased N-acetyl aspartate (neuro-axonal marker) and increased myo-inositol (astroglial marker) with a normal concentration of choline (membrane marker), which are compatible with the neuropathology of XP-A, consisting of a reduced number of neurons, and fibrillary astrogliosis with preservation of myelinated fibers...
July 12, 2018: Brain & Development
Henrique Rocha Mendonça, Juliana Nicolau Aranha Carvalho, Carla Andreia Abreu, Domethila Mariano de Souza Aguiar Dos Santos, Julia Rios Carvalho, Suelen Adriani Marques, Karin da Costa Calaza, Ana Maria Blanco Martinez
Diabetic retinopathy is the leading cause of acquired blindness in working-age individuals. Recent work has revealed that neurodegeneration occurs earlier than vascular insult and that distal optic nerve damage precedes retinal degeneration and vascular insult. Since we have shown that optic nerve degeneration is reduced after optic nerve crush in Galectin-3 knockout (Gal-3 -/-) mice, we decided to investigate whether Gal-3 -/- could relieve inflammation and preserve both neurons and the structure of the retina and optic nerve following 8 weeks of diabetes...
July 14, 2018: Brain Research
Shyue-Fang Battaglia-Hsu, Rose Ghemrawi, David Coelho, Natacha Dreumont, Pauline Mosca, Sébastien Hergalant, Guillaume Gauchotte, Jeffrey M Sequeira, Mariam Ndiongue, Rémi Houlgatte, Jean-Marc Alberto, Remy Umoret, Aurélie Robert, Justine Paoli, Martin Jung, Edward V Quadros, Jean-Louis Guéant
The molecular mechanisms that underlie the neurological manifestations of patients with inherited diseases of vitamin B12 (cobalamin) metabolism remain to date obscure. We observed transcriptomic changes of genes involved in RNA metabolism and endoplasmic reticulum stress in a neuronal cell model with impaired cobalamin metabolism. These changes were related to the subcellular mislocalization of several RNA binding proteins, including the ELAVL1/HuR protein implicated in neuronal stress, in this cell model and in patient fibroblasts with inborn errors of cobalamin metabolism and Cd320 knockout mice...
July 17, 2018: Nucleic Acids Research
Ilijas Jelcic, James V M Hanson, Sebastian Lukas, Konrad P Weber, Klara Landau, Misha Pless, Markus Reindl, Michael Weller, Roland Martin, Andreas Lutterotti, Sven Schippling
BACKGROUND: Recurrent optic neuritis (rON) associated with myelin oligodendrocyte glycoprotein (MOG)-specific antibodies has been initially reported to show a better clinical outcome than aquaporin-4 (AQP4)-seropositive ON in neuromyelitis optica spectrum disorder (NMOSD). Here, we characterize clinical and neuroimaging findings in severe cases of MOG antibody-positive and AQP4 antibody-negative bilateral rON. METHODS: Three male adults with rON (ages 18, 44, and 63 years) were evaluated with optical coherence tomography (OCT), MRI, cerebrospinal fluid (CSF), and serological studies...
July 13, 2018: Journal of Neuro-ophthalmology: the Official Journal of the North American Neuro-Ophthalmology Society
Afnan AlGhamdi, Muhammad Talal Alrifai, Abdullah I Al Hammad, Fuad Al Mutairi, Abdulrahman Alswaid, Wafaa Eyaid, Majid Alfadhel
Propionic acidemia is an inborn error of metabolism that is inherited in an autosomal recessive manner. It is characterized by a deficient propionyl-CoA carboxylase due to mutations in either of its beta or alpha subunits. In the literature, there is a clear association between propionic acidemia and epilepsy. In this cohort, we retrospectively reviewed the data of 14 propionic acidemia patients in Saudi Arabia and compared the findings to those of former studies. Six of the 14 (43%) patients developed epileptic seizure, mainly focal seizures...
January 1, 2018: Journal of Child Neurology
Melania Spadaro, Stephan Winklmeier, Eduardo Beltrán, Caterina Macrini, Romana Höftberger, Elisabeth Schuh, Franziska S Thaler, Lisa-Ann Gerdes, Sarah Laurent, Ramona Gerhards, Simone Brändle, Klaus Dornmair, Constanze Breithaupt, Markus Krumbholz, Markus Moser, Gurumoorthy Kirshnamoorthy, Frits Kamp, Dieter Jenne, Reinhard Hohlfeld, Tania Kümpfel, Hans Lassmann, Naoto Kawakami, Edgar Meinl
OBJECTIVE: Autoantibodies against myelin oligodendrocyte glycoprotein (MOG) occur in a proportion of patients with inflammatory demyelinating diseases of the CNS. We analyzed their pathogenic activity by affinity-purifying these Abs from patients and transferring them to experimental animals. METHODS: Patients with Abs to MOG were identified by cell-based assay. We determined the cross-reactivity to rodent MOG and determined the recognized MOG-epitopes. We produced the correctly folded extracellular domain of MOG and affinity-purified MOG-specific Abs from the blood of patients...
July 16, 2018: Annals of Neurology
Takayuki Fujii, Ryo Yamasaki, Kyoko Iinuma, Daisuke Tsuchimoto, Yoshinori Hayashi, Ban-Yu Saitoh, Takuya Matsushita, Mizuho A Kido, Shinichi Aishima, Hiroshi Nakanishi, Yusaku Nakabeppu, Jun-Ichi Kira
OBJECTIVES: To identify novel autoantibodies for neuropathic pain (NeP). METHODS: We screened autoantibodies that selectively bind to mouse unmyelinated C-fiber type dorsal root ganglion (DRG) neurons using tissue-based indirect immunofluorescence assays (IFA) with sera from 110 NeP patients with various inflammatory and allergic neurologic diseases or other neuropathies, and 50 controls without NeP including 20 healthy subjects and 30 patients with neurodegenerative diseases or systemic inflammatory diseases...
July 16, 2018: Annals of Neurology
A Sebastian López-Chiriboga, Masoud Majed, James Fryer, Divyanshu Dubey, Andrew McKeon, Eoin P Flanagan, Jiraporn Jitprapaikulsan, Naga Kothapalli, Jan-Mendelt Tillema, John Chen, Brian Weinshenker, Dean Wingerchuk, Jessica Sagen, Avi Gadoth, Vanda A Lennon, B Mark Keegan, Claudia Lucchinetti, Sean J Pittock
Importance: Recent studies have reported a higher relapse rate following an initial inflammatory demyelinating disorder in pediatric patients with persistent seropositivity of antibodies targeting myelin oligodendrocyte glycoprotein (MOG-IgG1). To date, the clinical implications of longitudinal MOG-IgG1 seropositivity using live cell assays with IgG1 secondary antibodies in adults after acute disseminated encephalomyelitis (ADEM) are unknown. Objective: To determine whether MOG-IgG1 serostatus (transient vs persistent) and titer change over time provide clinical utility in predicting the likelihood of relapse after ADEM...
July 16, 2018: JAMA Neurology
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