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Xiangbing Wu, Chandler L Walker, Qingbo Lu, Wei Wu, Daniel B Eddelman, Jonathan M Parish, Xiao-Ming Xu
Activation of RhoA/Rho kinase leads to growth cone collapse and neurite retraction. Although RhoA/Rho kinase inhibition has been shown to improve axon regeneration, remyelination and functional recovery, its role in neuronal cell death remains unclear. To determine whether RhoA/Rho kinase played a role in neuronal death after injury, we investigated the relationship between RhoA/Rho kinase and cytosolic phospholipase A2 (cPLA2), a lipase that mediates inflammation and cell death, using an in vitro neuronal death model and an in vivo contusive spinal cord injury model performed at the 10th thoracic (T10) vertebral level...
October 22, 2016: Molecular Neurobiology
Johanna Flygt, Fredrik Clausen, Niklas Marklund
BACKGROUND: Injury to the white matter may lead to impaired neuronal signaling and is commonly observed following traumatic brain injury (TBI). Although endogenous repair of TBI-induced white matter pathology is limited, oligodendrocyte progenitor cells (OPCs) may be stimulated to proliferate and regenerate functionally myelinating oligodendrocytes. Even though OPCs are present throughout the adult brain, little is known about their proliferative activity following axonal injury caused by TBI...
October 17, 2016: Restorative Neurology and Neuroscience
Hans Lassmann, Monika Bradl
One of the most frequent statements, provided in different variations in the introduction of experimental studies on multiple sclerosis (MS), is that "Multiple sclerosis is a demyelinating autoimmune disease and experimental autoimmune encephalomyelitis (EAE) is a suitable model to study its pathogenesis". However, so far, no single experimental model covers the entire spectrum of the clinical, pathological, or immunological features of the disease. Many different models are available, which proved to be highly useful for studying different aspects of inflammation, demyelination, remyelination, and neurodegeneration in the central nervous system...
October 20, 2016: Acta Neuropathologica
F Mashayekhi, Z Salehi
In the central nervous system (CNS) the main proteins of myelin are proteolipid protein (PLP), myelin basic protein (MBP), myelin oligodendrocyte glycoprotein (MOG) and CNPase. Myelin oligodendrocyte glycoprotein is a minor component of the myelin sheath, but is an important autoantigen linked to the pathogenesis of multiple sclerosis (MS). CNPase is expressed exclusively by oligodendrocytes in the CNS, and the appearance of CNPase seems to be one of the earliest events of oligodendrocyte differentiation and myelination...
2016: Folia Neuropathologica
Kms Kanhai, S C Goulooze, J Stevens, J L Hay, G Dent, A Verma, T Hankemeier, T de Boer, H Meijering, J C Chavez, A F Cohen, G J Groeneveld
Therapeutics promoting myelin synthesis may enhance recovery in demyelinating diseases, such as multiple sclerosis. However, no suitable method exists to quantify myelination. The turnover of galactosylceramide (myelin component) is indicative of myelination in mice, but its turnover has not been determined in humans. Here, six healthy subjects consumed 120 mL 70% D2 O daily for 70 days to label galactosylceramide. We then used mass spectrometry and compartmental modeling to quantify the turnover rate of galactosylceramide in cerebrospinal fluid...
October 15, 2016: Clinical and Translational Science
Zhimin Ou, Yuxia Sun, Li Lin, Nachun You, Xue Liu, Hongchao Li, Yanchen Ma, Lei Cao, Ying Han, Min Liu, Yaqi Deng, Luming Yao, Q Richard Lu, Ying Chen
: Demyelinating diseases, such as multiple sclerosis, are known to result from acute or chronic injury to the myelin sheath and inadequate remyelination; however, the underlying molecular mechanisms remain unclear. Here, we performed genome occupancy analysis by chromatin immunoprecipitation sequencing in oligodendrocytes in response to lysolecithin-induced injury and found that Olig2 and its downstream target Gpr17 are critical factors in regulating oligodendrocyte survival. After injury to oligodendrocytes, Olig2 was significantly upregulated and transcriptionally targeted the Gpr17 locus...
October 12, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
H C Hoyos, Mariel Marder, R Ulrich, V Gudi, M Stangel, G A Rabinovich, L A Pasquini, J M Pasquini
The aim of this work was to combine our previously published results with our new data to show how galectin-3 (Gal-3) controls myelin integrity and function, promotes oligodendroglial cell differentiation, and regulates microglial responses to limit cuprizone- (CPZ)-induced demyelination and foster remyelination. In this study, 8-week-old Gal-3-deficient (Lgals3 (-/-)) and wild type (WT) mice were fed a diet containing 0.2 % CPZ w/w for 6 weeks, after which CPZ was withdrawn in order to allow remyelination...
2016: Advances in Experimental Medicine and Biology
Adrián Sandoval-Hernández, María José Contreras, Jenny Jaramillo, Gonzalo Arboleda
During development and through adulthood, differentiation of diverse cell types is controlled by specific genetic and molecular programs for which transcription factors are master regulators of gene expression. Here, we present an overview of the role of nuclear receptors and their selective pharmacological modulators in oligodendrocytes linage, their role in myelination and remyelination and their potential use as a therapeutic strategy for demyelinating diseases. We discuss several aspects of nuclear receptors including: (1) the biochemistry of nuclear receptors superfamily; (2) their role on stem cells physiology, focusing in differentiation and cell removal; (3) the role of nuclear receptor in the oligodendrocytes cell linage, from oligodendrocyte progenitors cells to mature myelinating cells; and (4) the therapeutics opportunities of nuclear receptors for specific demyelinating diseases...
2016: Advances in Experimental Medicine and Biology
Arjun Saha, Susan Buntz, Paula Scotland, Li Xu, Pamela Noeldner, Sachit Patel, Amy Wollish, Aruni Gunaratne, Tracy Gentry, Jesse Troy, Glenn K Matsushima, Joanne Kurtzberg, Andrew E Balber
Microglia and monocytes play important roles in regulating brain remyelination. We developed DUOC-01, a cell therapy product intended for treatment of demyelinating diseases, from banked human umbilical cord blood (CB) mononuclear cells. Immunodepletion and selection studies demonstrated that DUOC-01 cells are derived from CB CD14(+) monocytes. We compared the ability of freshly isolated CB CD14(+) monocytes and DUOC-01 cells to accelerate remyelination of the brains of NOD/SCID/IL2Rγ(null) mice following cuprizone feeding-mediated demyelination...
August 18, 2016: JCI Insight
Davide Lecca, Davide Marangon, Giusy T Coppolino, Aida Menéndez Méndez, Annamaria Finardi, Gloria Dalla Costa, Vittorio Martinelli, Roberto Furlan, Maria P Abbracchio
In the mature central nervous system (CNS), oligodendrocytes provide support and insulation to axons thanks to the production of a myelin sheath. During their maturation to myelinating cells, oligodendroglial precursors (OPCs) follow a very precise differentiation program, which is finely orchestrated by transcription factors, epigenetic factors and microRNAs (miRNAs), a class of small non-coding RNAs involved in post-transcriptional regulation. Any alterations in this program can potentially contribute to dysregulated myelination, impaired remyelination and neurodegenerative conditions, as it happens in multiple sclerosis (MS)...
October 4, 2016: Scientific Reports
Majid Gharghani, Shima Dokoohaki, Amir Ghanbari, Naser Farhadi, Kazem Zibara, Saeid Khodadoust, Mohammad Parishani, Mehdi Ghavami Zadeh, Heibatollah Sadeghi
Melatonin has a beneficial role in adult rat models of multiple sclerosis (MS). In this study, melatonin treatment (10 mg/kg/d) was investigated in young age (5-6 weeks old) Lewis rat model of acute experimental autoimmune encephalomyelitis (EAE) followed by assessing serum levels of lactate and melatonin. Results showed that clinical outcomes were exacerbated in melatonin- (neurological score=6) versus PBS-treated EAE rats (score=5). Melatonin caused a significant increase in serum IFN-γ, in comparison to PBS-treated EAE rats whereas no considerable change in IL-4 levels were found, although they were significantly lower than those of controls...
October 3, 2016: Clinical and Experimental Pharmacology & Physiology
Jieun Jung, Jong-Wan Kim, Ho-Jin Moon, Jin Young Hong, Jung Keun Hyun
Neural stem cells (NSCs) have a high potency for differentiation to neurons and glial cells for replacement of damaged cells and paracrine effects for the regeneration and remyelination of host axons. Dental pulp is known to have a potential to differentiate into neural-like cells; therefore, dental pulp may be used as an autologous cell source for neural repair. In this study, we selectively expanded stem cells from human dental pulp in an initial culture using NSC media under xeno- and serum-free conditions...
2016: Stem Cells International
Feng Mei, Klaus Lehmann-Horn, Yun-An A Shen, Kelsey A Rankin, Karin J Stebbins, Daniel S Lorrain, Kara Pekarek, Sharon A Sagan, Lan Xiao, Cory Teuscher, H-Christian von Büdingen, Jürgen Wess, J Josh Lawrence, Ari J Green, Stephen Pj Fancy, Scott S Zamvil, Jonah R Chan
Demyelination in MS disrupts nerve signals and contributes to axon degeneration. While remyelination promises to restore lost function, it remains unclear whether remyelination will prevent axonal loss. Inflammatory demyelination is accompanied by significant neuronal loss in the experimental autoimmune encephalomyelitis (EAE) mouse model and evidence for remyelination in this model is complicated by ongoing inflammation, degeneration and possible remyelination. Demonstrating the functional significance of remyelination necessitates selectively altering the timing of remyelination relative to inflammation and degeneration...
2016: ELife
Alejandro Pinzon-Olejua, Cornelia Welte, Avinash Chekuru, Viktoria Bosak, Michael Brand, Stefan Hans, Claudia A O Stuermer
BACKGROUND: The conditional Cre/lox system has recently emerged as a valuable tool for studies on both embryonic and adult Zebrafish. Temporal control and site-specific recombination are achieved by using the ligand-inducible CreER(T2) and administration of the drug tamoxifen (TAM) or its active metabolite, 4-Hydroxytamoxifen (4-OHT). RESULTS: Here we report the generation of a transgenic Zebrafish line, which expresses an mCherry-tagged variant of CreER(T2) under the control of the myelin basic protein a (mbpa) promoter...
September 26, 2016: Developmental Dynamics: An Official Publication of the American Association of Anatomists
H El-Tahry, Hany E Marei, A Shams, M El-Shahat, H Abdelaziz, M Abd El-Kader
No abstract text is available yet for this article.
September 22, 2016: Tissue & Cell
T Duval, S Lévy, N Stikov, J Campbell, A Mezer, T Witzel, B Keil, V Smith, L L Wald, E Klawiter, J Cohen-Adad
The myelin g-ratio is defined as the ratio of the inner to the outer diameter of the myelin sheath. This ratio provides a measure of the myelin thickness that complements axon morphology (diameter and density) with high specificity for assessment of demyelination in diseases such as multiple sclerosis. Previous work has shown that an aggregate g-ratio map can be computed using a formula that combines axon and myelin density measured with quantitative MRI. In this work, we computed g-ratio weighted maps in the cervical spinal cord of nine healthy subjects...
September 21, 2016: NeuroImage
Yiting Zhou, Jing Zhang, Lu Wang, Ying Chen, Yushan Wan, Yang He, Lei Jiang, Jing Ma, Rujia Liao, Xiangnan Zhang, Liyun Shi, Zhenghong Qin, Yudong Zhou, Zhong Chen, Weiwei Hu
Subcortical ischemic vascular dementia (SIVD) caused by chronic cerebral hypoperfusion exhibits progressive white matter and cognitive impairments. However, its pathogenetic mechanisms are poorly understood. We investigated the role of interleukin-1β (IL-1β) and its receptor IL-1 receptor type 1 (IL-1R1) in an experimental SIVD model generated via right unilateral common carotid arteries occlusion (rUCCAO) in mice. We found that IL-1β expression was elevated in the corpus callosum at the early stages after rUCCAO...
September 20, 2016: Brain, Behavior, and Immunity
Samah Kalakh, Abdeslam Mouihate
There is compelling evidence that microglial activation negatively impacts neurogenesis. However, microglia have also been shown to promote recruitment of newly born neurons to injured areas of the gray matter. In the present study, we explored whether demyelination-triggered inflammation alters the process of neurogenesis in the white matter. A 2-μl solution of 0.04 % ethidium bromide was stereotaxically injected into the corpus callosum of adult male rats. Brain inflammation was dampened by daily injections of progesterone (5 mg/kg, s...
September 23, 2016: Molecular Neurobiology
Mohammad Gol, Davoud Ghorbanian, Samaneh Hassanzadeh, Mohammad Javan, Javad Mirnajafi-Zadeh, Maryam Ghasemi-Kasman
Recent evidence indicates that demyelination occurs in epilepsy patients and kindling animal models. Regarding the well-known literature on anti-inflammatory and myelin protective effects of fingolimod (FTY720) in multiple sclerosis patients and animal models, we hypostatized whether FTY720 administration could exert myelin protective effects in pentylenetetrazol (PTZ)-induced kindling model. To end this, animals received 0.3 or 1mg/kg dosage of FTY720, 1h before PTZ injections. In another approach, after achieving fully kindling stage, FTY720 was administrated i...
September 12, 2016: European Journal of Pharmaceutical Sciences
Salman Goudarzi, Andrea Rivera, Arthur M Butt, Sassan Hafizi
A key aim of therapy for multiple sclerosis (MS) is to promote the regeneration of oligodendrocytes and remyelination in the central nervous system (CNS). The present study provides evidence that the vitamin K-dependent protein growth arrest specific 6 (Gas6) promotes such repair in in vitro cultures of mouse optic nerve and cerebellum. We first determined expression of Gas6 and TAM (Tyro3, Axl, Mer) receptors in the mouse CNS, with all three TAM receptors increasing in expression through postnatal development, reaching maximal levels in the adult...
October 2016: ASN Neuro
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