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https://www.readbyqxmd.com/read/28224237/attempts-to-overcome-remyelination-failure-toward-opening-new-therapeutic-avenues-for-multiple-sclerosis
#1
REVIEW
Mahsa Motavaf, Majid Sadeghizadeh, Mohammad Javan
Multiple sclerosis (MS) is a chronic immune-mediated disorder of the central nervous system that results in destruction of the myelin sheath wrapped around the axons and eventual axon degeneration. The disease is pathologically heterogeneous; however, perhaps its most frustrating aspect is the lack of efficient regenerative response for remyelination. Current treatment strategies are based on anti-inflammatory or immunomodulatory medications that have the potential to reduce the numbers of newly evolving lesions...
February 21, 2017: Cellular and Molecular Neurobiology
https://www.readbyqxmd.com/read/28223915/oral-delivery-of-a-synthetic-sterol-reduces-axonopathy-and-inflammation-in-a-rodent-model-of-glaucoma
#2
Wendi S Lambert, Brian J Carlson, Cathryn R Formichella, Rebecca M Sappington, Clarence Ahlem, David J Calkins
Glaucoma is a group of optic neuropathies associated with aging and sensitivity to intraocular pressure (IOP). The disease is the leading cause of irreversible blindness worldwide. Early progression in glaucoma involves dysfunction of retinal ganglion cell (RGC) axons, which comprise the optic nerve. Deficits in anterograde transport along RGC axons to central visual structures precede outright degeneration, and preventing these deficits is efficacious at abating subsequent progression. HE3286 is a synthetic sterol derivative that has shown therapeutic promise in models of inflammatory disease and neurodegenerative disease...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28223179/biological-aspects-of-axonal-damage-in-glaucoma-a-brief-review
#3
REVIEW
Ernst R Tamm, C Ross Ethier, Claude Burgoyne, C Ross Ethier, Ernst R Tamm, Cheri Stowell, John E Dowling, Crawford Downs, Mark H Ellisman, Steven Fisher, Brad Fortune, Marcus Fruttiger, Tatjana Jakobs, Geoffrey Lewis, Claire H Mitchell, John Morrison, Sansar C Sharma, Ian Sigal, Michael Sofroniew, Lin Wang, Janey Wiggs, Samuel Wu, Richard H Masland
Intraocular pressure (IOP) is a critical risk factor in glaucoma, and the available evidence derived from experimental studies in primates and rodents strongly indicates that the site of IOP-induced axonal damage in glaucoma is at the optic nerve head (ONH). However, the mechanisms that cause IOP-induced damage at the ONH are far from understood. A possible sequence of events could originate with IOP-induced stress in the ONH connective tissue elements (peripapillary sclera, scleral canal and lamina cribrosa) that leads to an increase in biomechanical strain...
February 18, 2017: Experimental Eye Research
https://www.readbyqxmd.com/read/28222529/progressive-motor-deficit-is-mediated-by-the-denervation-of-neuromuscular-junctions-and-axonal-degeneration-in-transgenic-mice-expressing-mutant-p301s-tau-protein
#4
Zhuoran Yin, Femke Valkenburg, Betty E Hornix, Ietje Mantingh-Otter, Xingdong Zhou, Muriel Mari, Fulvio Reggiori, Debby Van Dam, Bart J L Eggen, Peter P De Deyn, Erik Boddeke
Tauopathies include a variety of neurodegenerative diseases associated with the pathological aggregation of hyperphosphorylated tau, resulting in progressive cognitive decline and motor impairment. The underlying mechanism for motor deficits related to tauopathy is not yet fully understood. Here, we use a novel transgenic tau mouse line, Tau 58/4, with enhanced neuron-specific expression of P301S mutant tau to investigate the motor abnormalities in association with the peripheral nervous system. Using stationary beam, gait, and rotarod tests, motor deficits were found in Tau 58/4 mice already 3 months after birth, which deteriorated during aging...
February 10, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28218988/toxicological-effects-during-and-following-persistent-insulin-induced-hypoglycaemia-in-healthy-euglycaemic-rats
#5
Vivi F H Jensen, Anne-Marie Mølck, Line O Berthelsen, Lene Alifrangis, Lene Andersen, Melissa Chapman, Jens Lykkesfeldt, Ingrid B Bøgh
New insulin analogues with a longer duration of action and a "peakless" pharmacokinetic profile have been developed to improve efficacy, safety and convenience for diabetic patients. During non-clinical development, according to regulatory guidelines, these analogues are tested in healthy euglycaemic rats rendering them persistently hypoglycaemic. Little is known about the effect of persistent (24 hr/day) insulin-induced hypoglycaemia (IIH) in rats, complicating interpretation of results in pre-clinical studies with new longer-acting insulin analogues...
February 20, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28217083/postnatal-loss-of-neuronal-and-glial-neurofascins-differentially-affects-node-of-ranvier-maintenance-and-myelinated-axon-function
#6
Anna M Taylor, Julia Saifetiarova, Manzoor A Bhat
Intricate molecular interactions between neurons and glial cells underlie the creation of unique domains that are essential for saltatory conduction of action potentials by myelinated axons. Previously, the cell surface adhesion molecule Neurofascin (Nfasc) has been shown to have a dual-role in the establishment of axonal domains from both the glial and neuronal interface. While the neuron-specific isoform of Neurofascin (NF186) is indispensable for clustering of voltage-gated sodium channels at nodes of Ranvier; the glial-specific isoform of Neurofascin (NF155) is required for myelinating glial cells to organize the paranodal domain...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28214960/axonal-disruption-in-white-matter-underlying-cortical-sulcus-tau-pathology-in-chronic-traumatic-encephalopathy
#7
Laurena Holleran, Joong Hee Kim, Mihika Gangolli, Thor Stein, Victor Alvarez, Ann McKee, David L Brody
Chronic traumatic encephalopathy (CTE) is a progressive degenerative disorder associated with repetitive traumatic brain injury. One of the primary defining neuropathological lesions in CTE, based on the first consensus conference, is the accumulation of hyperphosphorylated tau in gray matter sulcal depths. Post-mortem CTE studies have also reported myelin loss, axonal injury and white matter degeneration. Currently, the diagnosis of CTE is restricted to post-mortem neuropathological analysis. We hypothesized that high spatial resolution advanced diffusion MRI might be useful for detecting white matter microstructural changes directly adjacent to gray matter tau pathology...
February 18, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28214917/mtss1-promotes-maturation-and-maintenance-of-cerebellar-neurons-via-splice-variant-specific-effects
#8
Thorsten Sistig, Fanziska Lang, Sebastian Wrobel, Stephan L Baader, Karl Schilling, Britta Eiberger
Efficient coupling of the actin cytoskeleton to the cell membrane is crucial for histogenesis and maintenance of the nervous system. At this critical interface, BAR (Bin-Amphiphysin-Rvs) proteins regulate membrane bending, shown to be instrumental for mobility and morphogenesis of individual cells. Yet, the systemic significance of these proteins remains largely unexplored. Here, we probe the role of a prominent member of this protein family, the inverse-BAR protein Mtss1, for the development and function of a paradigmatic neuronal circuit, the cerebellar cortex...
February 18, 2017: Brain Structure & Function
https://www.readbyqxmd.com/read/28214515/igg-degrading-enzyme-of-streptococcus-pyogenes-ides-prevents-disease-progression-and-facilitates-improvement-in-a-rabbit-model-of-guillain-barr%C3%A3-syndrome
#9
Yuzhong Wang, Qiguang Shi, Hui Lv, Ming Hu, Weifang Wang, Quanquan Wang, Baojun Qiao, Guorong Zhang, Zhanyun Lv, Christian Kjellman, Sofia Järnum, Lena Winstedt, Yong Zhang, Jiao Wen, Yanlei Hao, Nobuhiro Yuki
Autoantibodies binding to peripheral nerves followed by complement deposition and membrane attack complex formation results in nerve damage in Guillain-Barré syndrome (GBS). Strategies to remove the pathogenic autoantibodies or block the complement deposition benefit most patients with GBS. Immunoglobulin G-degrading enzyme of Streptococcus pyogenes (IdeS) is a cysteine protease which cleaves IgG antibodies into F(ab')2 and Fc fragments. In this study, using a rabbit model of axonal GBS, acute motor axonal neuropathy (AMAN), we demonstrated that IdeS treatment significantly reduced the disruption of Nav channels as well as activated C3 deposition at the anterior spinal root nodes of Ranvier in AMAN rabbits...
February 16, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28213160/molecular-pathogenesis-of-peripheral-neuropathies-insights-from-drosophila-models
#10
REVIEW
Julia Bussmann, Erik Storkebaum
Peripheral neuropathies are characterized by degeneration of peripheral motor, sensory and/or autonomic axons, leading to progressive distal muscle weakness, sensory deficits and/or autonomic dysfunction. Acquired peripheral neuropathies, e.g., as a side effect of chemotherapy, are distinguished from inherited peripheral neuropathies (IPNs). Drosophila models for chemotherapy-induced peripheral neuropathy and several IPNs have provided novel insight into the molecular mechanisms underlying axonal degeneration...
February 14, 2017: Current Opinion in Genetics & Development
https://www.readbyqxmd.com/read/28208742/aav-vector-mediated-gene-delivery-to-substantia-nigra-dopamine-neurons-implications-for-gene-therapy-and-disease-models
#11
REVIEW
Katrina Albert, Merja H Voutilainen, Andrii Domanskyi, Mikko Airavaara
Gene delivery using adeno-associated virus (AAV) vectors is a widely used method to transduce neurons in the brain, especially due to its safety, efficacy, and long-lasting expression. In addition, by varying AAV serotype, promotor, and titer, it is possible to affect the cell specificity of expression or the expression levels of the protein of interest. Dopamine neurons in the substantia nigra projecting to the striatum, comprising the nigrostriatal pathway, are involved in movement control and degenerate in Parkinson's disease...
February 8, 2017: Genes
https://www.readbyqxmd.com/read/28208185/evaluation-of-progressive-visual-dysfunction-and-retinal-degeneration-in-patients-with-parkinson-s-disease
#12
Maria Satue, Maria J Rodrigo, Javier Obis, Elisa Vilades, Hector Gracia, Sofia Otin, Maria I Fuertes, Raquel Alarcia, Jose A Crespo, Vicente Polo, Jose M Larrosa, Luis E Pablo, Elena Garcia-Martin
Purpose: To quantify changes in visual function parameters and in the retinal nerve fiber layer and macular thickness over a 5-year period in patients with Parkinson's disease (PD). Methods: Thirty patients with PD and 30 healthy subjects underwent a complete ophthalmic evaluation, including assessment of visual acuity, contrast sensitivity vision, color vision, and retinal evaluation with spectral-domain optical coherence tomography (SD-OCT). All subjects were reevaluated after 5 years to quantify changes in visual function parameters, the retinal nerve fiber layer, and macular thickness...
February 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28203223/impaired-axonal-regeneration-in-diabetes-perspective-on-the-underlying-mechanism-from-in-vivo-and-in-vitro-experimental-studies
#13
REVIEW
Kazunori Sango, Hiroki Mizukami, Hidenori Horie, Soroku Yagihashi
Axonal regeneration after peripheral nerve injury is impaired in diabetes, but its precise mechanisms have not been elucidated. In this paper, we summarize the progress of research on altered axonal regeneration in animal models of diabetes and cultured nerve tissues exposed to hyperglycemia. Impaired nerve regeneration in animal diabetes can be attributed to dysfunction of neurons and Schwann cells, unfavorable stromal environment supportive of regenerating axons, and alterations of target tissues receptive to reinnervation...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28203148/dopamine-d1-receptor-immunoreactivity-on-fine-processes-of-gfap-positive-astrocytes-in-the-substantia-nigra-pars-reticulata-of-adult-mouse
#14
Katsuhiro Nagatomo, Sechiko Suga, Masato Saitoh, Masahito Kogawa, Kazuto Kobayashi, Yoshio Yamamoto, Katsuya Yamada
Substantia nigra pars reticulata (SNr), the major output nucleus of the basal ganglia, receives dopamine from dendrites extending from dopaminergic neurons of the adjacent nucleus pars compacta (SNc), which is known for its selective degeneration in Parkinson's disease. As a recipient for dendritically released dopamine, the dopamine D1 receptor (D1R) is a primary candidate due to its very dense immunoreactivity in the SNr. However, the precise location of D1R remains unclear at the cellular level in the SNr except for that reported on axons/axon terminals of presumably striatal GABAergic neurons...
2017: Frontiers in Neuroanatomy
https://www.readbyqxmd.com/read/28202549/relationships-between-type-2-diabetes-neuropathy-and-microvascular-dysfunction-evidence-from-patients-with-cryptogenic-axonal-polyneuropathy
#15
Anna L Emanuel, Mariska D Nieuwenhoff, Erica S Klaassen, Ajay Verma, Mark H H Kramer, Rob Strijers, Alexander F J E Vrancken, Etto Eringa, Geert Jan Groeneveld, Erik H Serné
OBJECTIVE: This study investigated whether the relationship between neuropathy and microvascular dysfunction in patients with type 2 diabetes is independent of diabetes-related factors. For this purpose, we compared skin microvascular function in patients with type 2 diabetes with that of patients with cryptogenic axonal polyneuropathy (CAP), a polyneuropathy of unknown etiology. RESEARCH DESIGN AND METHODS: Cross-sectional information was collected from 16 healthy controls (HCs), 16 patients with CAP, 15 patients with type 2 diabetes with polyneuropathy (DPN), and 11 patients with type 2 diabetes without polyneuropathy...
February 15, 2017: Diabetes Care
https://www.readbyqxmd.com/read/28196395/spread-of-tau-down-neural-circuits-precedes-synapse-and-neuronal-loss-in-the-rtgtauec-mouse-model-of-early-alzheimer-s-disease
#16
Eleanor K Pickett, Christopher M Henstridge, Elizabeth Allison, Rose Pitstick, Amy Pooler, Susanne Wegmann, George Carlson, Bradley T Hyman, Tara L Spires-Jones
Synaptic dysfunction and loss is the strongest pathological correlate of cognitive decline in Alzheimer's disease (AD) with increasing evidence implicating neuropathological tau protein in this process. Despite the knowledge that tau spreads through defined synaptic circuits, it is currently unknown whether synapse loss occurs before the accumulation of tau or as a consequence. To address this, we have used array tomography to examine an rTgTauEC mouse model expressing a P301L human tau transgene and a transgene labelling cytoplasm red (tdTomato) and presynaptic terminals green (Synaptophysin-EGFP)...
February 14, 2017: Synapse
https://www.readbyqxmd.com/read/28193690/lingo-1-regulates-oligodendrocyte-differentiation-through-the-cytoplasmic-gelsolin-signaling-pathway
#17
Zhaohui Shao, Xinhua Lee, Guanrong Huang, Guoqing Sheng, Christopher E Henderson, Daniel Louvard, Jiho Sohn, Blake Pepinsky, Sha Mi
Differentiation and maturation of oligodendrocyte progenitor cells (OPCs) involve the assembly and disassembly of actin microfilaments. How actin dynamics is regulated during this process remains poorly understood. Leucine rich repeat and Immunoglobulin-like domain-containing Nogo receptor interacting protein 1(LINGO-1) is a negative regulator of OPC differentiation. We discovered that anti-LINGO-1 antibody promoted OPC differentiation was accompanied by upregulation of cytoplasmic gelsolin (cGSN), an abundant actin-severing protein involved in the depolymerization of actin filaments...
February 13, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28193453/energy-and-the-alzheimer-brain
#18
REVIEW
Mortimer Mamelak
The high energy demands of the poorly myelinated long axon hippocampal and cortical neurons render these neurons selectively vulnerable to degeneration in Alzheimer's disease. However, pathology engages all of the major elements of the neurovascular unit of the mature Alzheimer brain, the neurons, glia and blood vessels. Neurons present with retrograde degeneration of the axodendritic tree, capillaries with string vessels and markedly reduced densities and glia with signs of inflammatory activation. The neurons, capillaries and astrocytes of the mature Alzheimer brain harbor structurally defective mitochondria...
February 11, 2017: Neuroscience and Biobehavioral Reviews
https://www.readbyqxmd.com/read/28192539/optical-coherence-tomography-segmentation-analysis-in-relapsing-remitting-versus-progressive-multiple-sclerosis
#19
Raed Behbehani, Abdullah Abu Al-Hassan, Ali Al-Salahat, Devarajan Sriraman, J D Oakley, Raed Alroughani
INTRODUCTION: Optical coherence tomography (OCT) with retinal segmentation analysis is a valuable tool in assessing axonal loss and neuro-degeneration in multiple sclerosis (MS) by in-vivo imaging, delineation and quantification of retinal layers. There is evidence of deep retinal involvement in MS beyond the inner retinal layers. The ultra-structural retinal changes in MS in different MS phenotypes can reflect differences in the pathophysiologic mechanisms. There is limited data on the pattern of deeper retinal layer involvement in progressive MS (PMS) versus relapsing remitting MS (RRMS)...
2017: PloS One
https://www.readbyqxmd.com/read/28188715/-multiple-sclerosis-current-immunological-aspects
#20
Carlos Cuevas-García
Multiple sclerosis is the most common inflammatory, chronic and degenerative condition of the central nervous system, and represents the first cause of disability in young adults. In Mexico, 11 to 20 out of every 100 000 people suffer from this disease. The causes of multiple sclerosis remain unknown, but several theories have been proposed: the interaction of environmental factors, viral infectious factors and genetic and immune susceptibility of each individual patient, which induce an autoimmune response and promote neuronal/axonal degeneration...
January 2017: Revista Alergia Mexico: Organo Oficial de la Sociedad Mexicana de Alergia e Inmunología, A.C
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