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https://www.readbyqxmd.com/read/27899315/injury-stimulated-sonic-hedgehog-expression-in-microglia-contributes-to-neuroinflammatory-response-in-the-mptp-model-of-parkinson-s-disease
#1
Jung Hwi Lee, Young Cheul Chung, Eugene Bok, Hankyu Lee, Sue Hee Huh, Ji Eun Lee, Byung Kwan Jin, Hyuk Wan Ko
Parkinson's disease (PD) is a progressive neurodegenerative disorder in which dopamine (DA) neurons in the substantia nigra pars compacta (SNpc) region are selectively destroyed. Sonic hedgehog (Shh) has been well known to play a key role in a variety of processes such as embryogenesis, cell proliferation and protection, and tissue repair during inflammation. However, the evidences for the innate role of Shh in adult brain injury are presently lacking and studies have been needed to unveil the importance of Shh in the process of neurodegeneration...
November 26, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27858314/genetically-dissecting-p2rx7-expression-within-the-central-nervous-system-using-conditional-humanized-mice
#2
Michael W Metzger, Sandra M Walser, Fernando Aprile-Garcia, Nina Dedic, Alon Chen, Florian Holsboer, Eduardo Arzt, Wolfgang Wurst, Jan M Deussing
The purinergic P2X7 receptor (P2X7R) has attracted considerable interest as a potential target for various central nervous system (CNS) pathologies including affective and neurodegenerative disorders. To date, the distribution and cellular localization of the P2X7R in the brain are not fully resolved and a matter of debate mainly due to the limitations of existing tools. However, this knowledge should be a prerequisite for understanding the contribution of the P2X7R to brain disease. Here, we generated a genetic mouse model by humanizing the P2X7R in the mouse as mammalian model organism...
November 17, 2016: Purinergic Signalling
https://www.readbyqxmd.com/read/27853976/tapered-tip-capillary-electrophoresis-nano-electrospray-ionization-mass-spectrometry-for-ultrasensitive-proteomics-the-mouse-cortex
#3
Sam B Choi, Marta Zamarbide, M Chiara Manzini, Peter Nemes
Ultrasensitive characterization of the proteome raises the potential to understand how differential gene expression orchestrates cell heterogeneity in the brain. Here, we report a microanalytical capillary electrophoresis nano-flow electrospray ionization (CE-nanoESI) interface for mass spectrometry to enable the measurement of limited amounts of proteins in the mouse cortex. Our design integrates a custom-built CE system to a tapered-tip metal emitter in a co-axial sheath-flow configuration. This interface can be constructed in <15 min using readily available components, facilitating broad adaptation...
November 16, 2016: Journal of the American Society for Mass Spectrometry
https://www.readbyqxmd.com/read/27832161/molecular-analysis-of-stromal-cells-induced-neural-differentiation-of-mouse-embryonic-stem-cells
#4
Ramila Joshi, James Carlton Buchanan, Sailaja Paruchuri, Nathan Morris, Hossein Tavana
Deriving specific neural cells from embryonic stem cells (ESCs) is a promising approach for cell replacement therapies of neurodegenerative diseases. When co-cultured with certain stromal cells, mouse ESCs (mESCs) differentiate efficiently to neural cells. In this study, a comprehensive gene and protein expression analysis of differentiating mESCs is performed over a two-week culture period to track temporal progression of cells from a pluripotent state to specific terminally-differentiated neural cells such as neurons, astrocytes, and oligodendrocytes...
2016: PloS One
https://www.readbyqxmd.com/read/27829126/oligodendrogenesis-after-traumatic-brain-injury
#5
REVIEW
Hajime Takase, Kazuo Washida, Kazuhide Hayakawa, Ken Arai, Xiaoying Wang, Eng H Lo, Josephine Lok
White matter injury is an important contributor to long term motor and cognitive dysfunction after traumatic brain injury. During brain trauma, acceleration, deceleration, torsion, and compression forces often cause direct damage to the axon tracts, and pathways that are triggered by the initial injury can trigger molecular events that result in secondary axon degeneration. White matter injury is often associated with altered mental status, memory deficits, motor or autonomic dysfunction, and contribute to the development of chronic neurodegenerative diseases...
November 6, 2016: Behavioural Brain Research
https://www.readbyqxmd.com/read/27808258/significant-glial-alterations-in-response-to-iron-loading-in-a-novel-organotypic-hippocampal-slice-culture-model
#6
Sinead Healy, Jill McMahon, Peter Owens, Una FitzGerald
Aberrant iron deposition in the brain is associated with neurodegenerative disorders including Multiple Sclerosis, Alzheimer's disease and Parkinson's disease. To study the collective response to iron loading, we have used hippocampal organotypic slices as a platform to develop a novel ex vivo model of iron accumulation. We demonstrated differential uptake and toxicity of iron after 12 h exposure to 10 μM ferrous ammonium sulphate, ferric citrate or ferrocene. Having established the supremacy of ferrocene in this model, the cultures were then loaded with 0...
November 3, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27798140/conditional-deletion-of-the-l-type-calcium-channel-cav1-2-in-oligodendrocyte-progenitor-cells-affects-postnatal-myelination-in-mice
#7
Veronica T Cheli, Diara A Santiago González, Tenzing Namgyal Lama, Vilma Spreuer, Vance Handley, Geoffrey G Murphy, Pablo M Paez
: To determine whether L-type voltage-operated Ca(2+) channels (L-VOCCs) are required for oligodendrocyte progenitor cell (OPC) development, we generated an inducible conditional knock-out mouse in which the L-VOCC isoform Cav1.2 was postnatally deleted in NG2-positive OPCs. A significant hypomyelination was found in the brains of the Cav1.2 conditional knock-out (Cav1.2(KO)) mice specifically when the Cav1.2 deletion was induced in OPCs during the first 2 postnatal weeks. A decrease in myelin proteins expression was visible in several brain structures, including the corpus callosum, cortex, and striatum, and the corpus callosum of Cav1...
October 19, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27780064/axonal-degeneration-ripk1-multitasking-in-als
#8
Kristin Politi, Serge Przedborski
A recent study reports that microglia and oligodendrocytes promote motor neuron degeneration by inducing inflammation and necroptosis in a manner dependent on receptor-interacting kinase 1 (RIPK1). These findings could be significant for our understanding of the neurobiology and treatment of neurodegenerative diseases like amyotrophic lateral sclerosis.
October 24, 2016: Current Biology: CB
https://www.readbyqxmd.com/read/27779191/25-hydroxycholesterol-contributes-to-cerebral-inflammation-of-x-linked-adrenoleukodystrophy-through-activation-of-the-nlrp3-inflammasome
#9
Jiho Jang, Sangjun Park, Hye Jin Hur, Hyun-Ju Cho, Inhwa Hwang, Yun Pyo Kang, Isak Im, Hyunji Lee, Eunju Lee, Wonsuk Yang, Hoon-Chul Kang, Sung Won Kwon, Je-Wook Yu, Dong-Wook Kim
X-linked adrenoleukodystrophy (X-ALD), caused by an ABCD1 mutation, is a progressive neurodegenerative disorder associated with the accumulation of very long-chain fatty acids (VLCFA). Cerebral inflammatory demyelination is the major feature of childhood cerebral ALD (CCALD), the most severe form of ALD, but its underlying mechanism remains poorly understood. Here, we identify the aberrant production of cholesterol 25-hydroxylase (CH25H) and 25-hydroxycholesterol (25-HC) in the cellular context of CCALD based on the analysis of ALD patient-derived induced pluripotent stem cells and ex vivo fibroblasts...
October 25, 2016: Nature Communications
https://www.readbyqxmd.com/read/27764517/effect-of-recombinant-lactococcus-lactis-producing-myelin-peptides-on-neuroimmunological-changes-in-rats-with-experimental-allergic-encephalomyelitis
#10
K Kasarełło, A Szczepankowska, B Kwiatkowska-Patzer, A W Lipkowski, R Gadamski, D Sulejczak, M Łachwa, M Biały, J Bardowski
Multiple sclerosis (MS) is a human autoimmune neurodegenerative disease with an unknown etiology. Despite various therapies, there is no effective cure for MS. Since the mechanism of the disease is based on autoreactive T-cell responses directed against myelin antigens, oral tolerance is a promising approach for the MS treatment. Here, the experiments were performed to assess the impact of oral administration of recombinant Lactococcus lactis producing encephalogenic fragments of three myelin proteins: myelin basic protein, proteolipid protein, and myelin oligodendrocyte glycoprotein, on neuroimmunological changes in rats with experimental allergic encephalomyelitis (EAE) - an animal model of MS...
2016: Folia Neuropathologica
https://www.readbyqxmd.com/read/27762676/canonical-micrornas-enable-differentiation-protect-against-dna-damage-and-promote-cholesterol-biosynthesis-in-neural-stem-cells
#11
Zhong Liu, Cheng Zhang, Alireza Khodadadi-Jamayran, Lam Dang, Xiaosi Han, Kitai Kim, Hu Li, Rui Zhao
Neural stem cells (NSCs) have the capacity to differentiate into neurons, astrocytes, and oligodendrocytes, and therefore represent a promising donor tissue source for treating neurodegenerative diseases and repairing injuries of the nervous system. However, it remains unclear how canonical microRNAs (miRNAs), the subset of miRNAs requiring the Drosha-Dgcr8 microprocessor and the type III RNase Dicer for biogenesis, regulate NSCs. In this study, we established and characterized <i>Dgcr8</i><sup>-/-</sup> NSCs from conditionally <i>Dgcr8</i>-disrupted mouse embryonic brain...
October 20, 2016: Stem Cells and Development
https://www.readbyqxmd.com/read/27748825/identification-and-bioinformatic-analysis-of-dysregulated-micrornas-in-human-oligodendroglial-cells-infected-with-borna-disease-virus
#12
Hong Zhang, Peng He, Rongzhong Huang, Lin Sun, Siwen Liu, Jingjing Zhou, Yujie Guo, Deyu Yang, Peng Xie
MicroRNAs (miRNAs) are recognized as important regulators of gene expression via translational depression or mRNA degradation. Previously, dysregulated miRNAs have been found in neurodegenerative and neuropsychiatric disorders. Borna disease virus (BDV) is a neurotropic, negative single‑stranded RNA virus, which may be a cause of human neuropsychiatric disease. BDV is regarded as an ideal model to analyze the molecular mechanisms of mental disorders caused by viral infection. In the present study, 10 miRNAs were dysregulated in human oligodendrocytes (OL cells) infected with the BDV strain, Hu‑H1 (OL/BDV)...
November 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27717881/n-acetylaspartate-supports-the-energetic-demands-of-developmental-myelination-via-oligodendroglial-aspartoacylase
#13
Jeremy S Francis, Ireneusz Wojtas, Vladimir Markov, Steven J Gray, Thomas J McCown, R Jude Samulski, Larissa T Bilaniuk, Dah-Jyuu Wang, Darryl C De Vivo, Christopher G Janson, Paola Leone
Breakdown of neuro-glial N-acetyl-aspartate (NAA) metabolism results in the failure of developmental myelination, manifest in the congenital pediatric leukodystrophy Canavan disease caused by mutations to the sole NAA catabolizing enzyme aspartoacylase. Canavan disease is a major point of focus for efforts to define NAA function, with available evidence suggesting NAA serves as an acetyl donor for fatty acid synthesis during myelination. Elevated NAA is a diagnostic hallmark of Canavan disease, which contrasts with a broad spectrum of alternative neurodegenerative contexts in which levels of NAA are inversely proportional to pathological progression...
December 2016: Neurobiology of Disease
https://www.readbyqxmd.com/read/27714695/regulation-of-oligodendrocyte-differentiation-and-myelination-by-nuclear-receptors-role-in-neurodegenerative-disorders
#14
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
https://www.readbyqxmd.com/read/27714685/microglia-function-in-the-normal-brain
#15
Rommy von Bernhardi, Florencia Heredia, Nicole Salgado, Paola Muñoz
The activation of microglia has been recognized for over a century by their morphological changes. Long slender microglia acquire a short sturdy ramified shape when activated. During the past 20 years, microglia have been accepted as an essential cellular component for understanding the pathogenic mechanism of many brain diseases, including neurodegenerative diseases. More recently, functional studies and imaging in mouse models indicate that microglia are active in the healthy central nervous system. It has become evident that microglia release several signal molecules that play key roles in the crosstalk among brain cells, i...
2016: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/27698367/mir-125a-3p-timely-inhibits-oligodendroglial-maturation-and-is-pathologically-up-regulated-in-human-multiple-sclerosis
#16
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
https://www.readbyqxmd.com/read/27678346/shared-and-distinct-patterns-of-oligodendroglial-response-in-%C3%AE-synucleinopathies-and-tauopathies
#17
Zdenek Rohan, Ivan Milenkovic, Mirjam I Lutz, Radoslav Matej, Gabor G Kovacs
Pathological protein deposits in oligodendroglia are common but variable features of various neurodegenerative conditions. To evaluate oligodendrocyte response in neurodegenerative diseases (NDDs) with different extents of oligodendroglial protein deposition we performed immunostaining for tubulin polymerization-promoting protein p25α (TPPP/p25α), α-synuclein (α-syn), phospho-tau, ubiquitin, myelin basic protein, and the microglial marker HLA-DR. We investigated cases of multiple system atrophy ([MSA] n = 10), Lewy body disease ([LBD] n = 10), globular glial tauopathy ([GGT] n = 7) and progressive supranuclear palsy ([PSP] n = 10)...
September 26, 2016: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/27671624/laquinimod-arrests-experimental-autoimmune-encephalomyelitis-by-activating-the-aryl-hydrocarbon-receptor
#18
Joel Kaye, Victor Piryatinsky, Tal Birnberg, Tal Hingaly, Emanuel Raymond, Rina Kashi, Einat Amit-Romach, Ignacio S Caballero, Fadi Towfic, Mark A Ator, Efrat Rubinstein, Daphna Laifenfeld, Aric Orbach, Doron Shinar, Yael Marantz, Iris Grossman, Volker Knappertz, Michael R Hayden, Ralph Laufer
Laquinimod is an oral drug currently being evaluated for the treatment of relapsing, remitting, and primary progressive multiple sclerosis and Huntington's disease. Laquinimod exerts beneficial activities on both the peripheral immune system and the CNS with distinctive changes in CNS resident cell populations, especially astrocytes and microglia. Analysis of genome-wide expression data revealed activation of the aryl hydrocarbon receptor (AhR) pathway in laquinimod-treated mice. The AhR pathway modulates the differentiation and function of several cell populations, many of which play an important role in neuroinflammation...
October 11, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27661457/is-involvement-of-inflammation-underestimated-in-pelizaeus-merzbacher-disease
#19
Antoine Marteyn, Anne Baron-Van Evercooren
Pelizaeus-Merzbacher disease (PMD) is a severe hypomyelinating leukodystrophy resulting from proteolipid protein 1 gene (PLP1) mutations leading to oligodendrocyte loss. While neuroinflammation has recently become a common feature and actor in neurodegenerative diseases, the involvement of inflammation in PMD physiopathology is still highly debated despite evidence for strong astrogliosis and microglial cell activation. Activation of the innate immune system, and more particularly, of microglia and astrocytes, is mostly associated with the deleterious role of neuroinflammation...
December 2016: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/27641725/activation-of-the-astrocytic-nrf2-are-system-ameliorates-the-formation-of-demyelinating-lesions-in-a-multiple-sclerosis-animal-model
#20
T Draheim, A Liessem, M Scheld, F Wilms, M Weißflog, B Denecke, T W Kensler, A Zendedel, C Beyer, M Kipp, C J Wruck, A Fragoulis, T Clarner
Oxidative stress critically contributes to the pathogenesis of a variety of neurodegenerative diseases such as multiple sclerosis. Astrocytes are the main regulators of oxidative homeostasis in the brain and dysregulation of these cells likely contributes to the accumulation of oxidative damage. The nuclear factor erythroid 2-related factor 2 (Nrf2) is the main transcriptional regulator of the anti-oxidant stress defense. In this study, we elucidate the effects of astrocytic Nrf2-activation on brain-intrinsic inflammation and lesion development...
September 19, 2016: Glia
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