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https://www.readbyqxmd.com/read/28101749/twenty-seven-years-of-cerebral-pyruvate-recycling
#1
Sebastián Cerdán
Cerebral pyruvate recycling is a metabolic pathway deriving carbon skeletons and reducing equivalents from mitochondrial oxaloacetate and malate, to the synthesis of mitochondrial and cytosolic pyruvate, lactate and alanine. The pathway allows both, to provide the tricarboxylic acid cycle with pyruvate molecules produced from alternative substrates to glucose and, to generate reducing equivalents necessary for the operation of NADPH requiring processes. At the cellular level, pyruvate recycling involves the activity of malic enzyme, or the combined activities of phosphoenolpyruvate carboxykinase and pyruvate kinase, as well as of those transporters of the inner mitochondrial membrane exchanging the corresponding intermediates...
January 18, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28100749/promoted-interaction-of-c-ebp%C3%AE-with-demethylated-cxcr3-gene-promoter-contributes-to-neuropathic-pain-in-mice
#2
Bao-Chun Jiang, Li-Na He, Xiao-Bo Wu, Hui Shi, Wen-Wen Zhang, Zhi-Jun Zhang, De-Li Cao, Chun-Hua Li, Jun Gu, Yong-Jing Gao
: DNA methylation has been implicated in the pathogenesis of chronic pain. However, the specific genes regulated by DNA methylation under neuropathic pain condition remain largely unknown. Here we investigated how chemokine receptor CXCR3 is regulated by DNA methylation and how it contributes to neuropathic pain induced by spinal nerve ligation (SNL) in mice. SNL increased Cxcr3 mRNA and protein expression in the neurons of the spinal cord. Meanwhile, the CpG (5'-cytosine-phosphate-guanine-3') island in the Cxcr3 gene promoter region was demethylated, and the expression of DNA methyltransferase 3b (DNMT3b) was decreased...
January 18, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28100736/methyl-cpg-binding-protein-mbd1-regulates-neuronal-lineage-commitment-through-maintaining-adult-neural-stem-cell-identity
#3
Emily M Jobe, Yu Gao, Brian E Eisinger, Janessa K Mladucky, Charles C Giuliani, Laurel E Kelnhofer, Xinyu Zhao
: Methyl-CpG-binding domain 1 (MBD1) belongs to a family of methyl-CpG-binding proteins that are epigenetic "readers" linking DNA methylation to transcriptional regulation. MBD1 is expressed in neural stem cells residing in the dentate gyrus of the adult hippocampus (aNSCs) and MBD1 deficiency leads to reduced neuronal differentiation, impaired neurogenesis, learning deficits, and autism-like behaviors in mice; however, the precise function of MBD1 in aNSCs remains unexplored. Here, we show that MBD1 is important for maintaining the integrity and stemness of NSCs, which is critical for their ability to generate neurons...
January 18, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28100653/minocycline-blocks-glial-cell-activation-and-ventilatory-acclimatization-to-hypoxia
#4
Jennifer Ann Stokes, Tara Elizabeth Arbogast, Esteban A Moya, Zhenxing Fu, Frank L Powell
Ventilatory acclimatization to hypoxia (VAH) is the time-dependent increase in ventilation, which persists upon return to normoxia, and involves plasticity in both central nervous system respiratory centers and peripheral chemoreceptors. We investigated the role of glial cells in VAH in male Sprague Dawley rats using minocycline, an antibiotic that inhibits microglia activation and has anti-inflammatory properties, and barometric pressure plethysmography to measure ventilation. Rats received either minocycline (45mg/kg, i...
January 18, 2017: Journal of Neurophysiology
https://www.readbyqxmd.com/read/28100644/multicellular-hypothesis-for-the-pathogenesis-of-alzheimer-s-disease
#5
Edward J Goetzl, Bruce L Miller
Extensive abnormal interactions among microglia, astrocytes, and neurons of the CNS have been observed in proteinopathic neurodegenerative dementias of the elderly. These multicellular interactions are initiated by insoluble tangles of phosphorylated tau protein and plaques of amyloid peptides. Most research has focused on these neurotoxic proteins, but much less is known about the pathogenic roles of the responding resident and recruited neural cells. Principal interactions among the major 3 sets of CNS cells are herein considered at several levels in relation to cellular phenotypic alterations, mechanisms of cellular communication, and extent of involvement in the pathogenesis of Alzheimer's disease and related proteinopathic dementias...
January 18, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28099881/mesencephalic-astrocyte-derived-neurotrophic-factor-alleviated-6-ohda-induced-cell-damage-via-ros-ampk-mtor-mediated-autophagic-inhibition
#6
Jingxing Zhang, Qiong Cai, Ming Jiang, Yigang Liu, Hua Gu, Jia Guo, Hui Sun, Jianmin Fang, Lingjing Jin
Autophagy and apoptosis are commonly involved in the dopaminergic neuron damage in the pathogenesis of Parkinson's disease. Recently, the autophagy pathway is thought to be critical to the process of PD. Therefore, the regulation of autophagy may be a potential strategy for PD treatment. Mesencephalic astrocyte-derived neurotrophic factor (MANF) has been reported to have neuroprotective effects through anti-apoptosis, anti-oxidative, and anti-inflammatory mechanisms in PD. In this study, we investigated the role of autophagy system in MANF-mediated neuroprotection against 6-hydroxydopamine (6-OHDA)-induced neurotoxicity...
January 15, 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/28099855/primary-cell-culture-of-live-neurosurgically-resected-aged-adult-human-brain-cells-and-single-cell-transcriptomics
#7
Jennifer M Spaethling, Young-Ji Na, Jaehee Lee, Alexandra V Ulyanova, Gordon H Baltuch, Thomas J Bell, Steven Brem, H Isaac Chen, Hannah Dueck, Stephen A Fisher, Marcela P Garcia, Mugdha Khaladkar, David K Kung, Timothy H Lucas, Donald M O'Rourke, Derek Stefanik, Jinhui Wang, John A Wolf, Tamas Bartfai, M Sean Grady, Jai-Yoon Sul, Junhyong Kim, James H Eberwine
Investigation of human CNS disease and drug effects has been hampered by the lack of a system that enables single-cell analysis of live adult patient brain cells. We developed a culturing system, based on a papain-aided procedure, for resected adult human brain tissue removed during neurosurgery. We performed single-cell transcriptomics on over 300 cells, permitting identification of oligodendrocytes, microglia, neurons, endothelial cells, and astrocytes after 3 weeks in culture. Using deep sequencing, we detected over 12,000 expressed genes, including hundreds of cell-type-enriched mRNAs, lncRNAs and pri-miRNAs...
January 17, 2017: Cell Reports
https://www.readbyqxmd.com/read/28099854/single-cell-transcriptomic-analysis-defines-heterogeneity-and-transcriptional-dynamics-in-the-adult-neural-stem-cell-lineage
#8
Ben W Dulken, Dena S Leeman, Stéphane C Boutet, Katja Hebestreit, Anne Brunet
Neural stem cells (NSCs) in the adult mammalian brain serve as a reservoir for the generation of new neurons, oligodendrocytes, and astrocytes. Here, we use single-cell RNA sequencing to characterize adult NSC populations and examine the molecular identities and heterogeneity of in vivo NSC populations. We find that cells in the NSC lineage exist on a continuum through the processes of activation and differentiation. Interestingly, rare intermediate states with distinct molecular profiles can be identified and experimentally validated, and our analysis identifies putative surface markers and key intracellular regulators for these subpopulations of NSCs...
January 17, 2017: Cell Reports
https://www.readbyqxmd.com/read/28099414/neurotoxic-reactive-astrocytes-are-induced-by-activated-microglia
#9
Shane A Liddelow, Kevin A Guttenplan, Laura E Clarke, Frederick C Bennett, Christopher J Bohlen, Lucas Schirmer, Mariko L Bennett, Alexandra E Münch, Won-Suk Chung, Todd C Peterson, Daniel K Wilton, Arnaud Frouin, Brooke A Napier, Nikhil Panicker, Manoj Kumar, Marion S Buckwalter, David H Rowitch, Valina L Dawson, Ted M Dawson, Beth Stevens, Ben A Barres
Reactive astrocytes are strongly induced by central nervous system (CNS) injury and disease, but their role is poorly understood. Here we show that a subtype of reactive astrocytes, which we termed A1, is induced by classically activated neuroinflammatory microglia. We show that activated microglia induce A1 astrocytes by secreting Il-1α, TNF and C1q, and that these cytokines together are necessary and sufficient to induce A1 astrocytes. A1 astrocytes lose the ability to promote neuronal survival, outgrowth, synaptogenesis and phagocytosis, and induce the death of neurons and oligodendrocytes...
January 18, 2017: Nature
https://www.readbyqxmd.com/read/28098781/distinct-neurotoxicity-profile-of-listeriolysin-o-from-listeria-monocytogenes
#10
Jana Maurer, Sabrina Hupp, Carolin Bischoff, Christina Foertsch, Timothy J Mitchell, Trinad Chakraborty, Asparouh I Iliev
Cholesterol-dependent cytolysins (CDCs) are protein toxins that originate from Gram-positive bacteria and contribute substantially to their pathogenicity. CDCs bind membrane cholesterol and build prepores and lytic pores. Some effects of the toxins are observed in non-lytic concentrations. Two pathogens, Streptococcus pneumoniae and Listeria monocytogenes, cause fatal bacterial meningitis, and both produce toxins of the CDC family-pneumolysin and listeriolysin O, respectively. It has been demonstrated that pneumolysin produces dendritic varicosities (dendrite swellings) and dendritic spine collapse in the mouse neocortex, followed by synaptic loss and astrocyte cell shape remodeling without elevated cell death...
January 13, 2017: Toxins
https://www.readbyqxmd.com/read/28098764/iqgap1-in-podosomes-invadosomes-is-involved-in-the-progression-of-glioblastoma-multiforme-depending-on-the-tumor-status
#11
Deborah Rotoli, Natalia Dolores Pérez-Rodríguez, Manuel Morales, María Del Carmen Maeso, Julio Ávila, Ali Mobasheri, Pablo Martín-Vasallo
Glioblastoma multiforme (GBM) is the most frequent and aggressive primary brain tumor. GBM is formed by a very heterogeneous astrocyte population, neurons, neovascularization and infiltrating myeloid cells (microglia and monocyte derived macrophages). The IQGAP1 scaffold protein interacts with components of the cytoskeleton, cell adhesion molecules, and several signaling molecules to regulate cell morphology and motility, cell cycle and other cellular functions. IQGAP1 overexpression and delocalization has been observed in several tumors, suggesting a role for this protein in cell proliferation, transformation and invasion...
January 13, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28098158/pericytes-from-mesenchymal-stem-cells-as-a-model-for-the-blood-brain-barrier
#12
Xiaohe Tian, Oliver Brookes, Giuseppe Battaglia
Blood brain-barrier (BBB) in vitro models have been widely reported in studies of the BBB phenotype. However, established co-culture systems involve brain endothelial cells, astrocytes, neurons and pericytes, and therefore are often consuming and technically challenging. Here we use mesenchymal system cells (MSC) as a potential substitute for pericytes in a BBB model. Both MSC and pericyte markers in 2D culture environment were evaluated on different extracellular matrix compositions. Further experiments indicated that MSC contributed in a similar manner to pericytes in a co-cultured 3D model on increasing trans-endothelial electric resistance (TEER) and decreasing permeability against macromolecules...
January 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28097486/the-therapeutic-effectiveness-of-delayed-fetal-spinal-cord-tissue-transplantation-on-respiratory-function-following-mid-cervical-spinal-cord-injury
#13
Chia-Ching Lin, Sih-Rong Lai, Yu-Han Shao, Chun-Lin Chen, Kun-Ze Lee
Respiratory impairment due to damage of the spinal respiratory motoneurons and interruption of the descending drives from brainstem premotor neurons to spinal respiratory motoneurons is the leading cause of morbidity and mortality following cervical spinal cord injury. The present study was designed to evaluate the therapeutic effectiveness of delayed transplantation of fetal spinal cord (FSC) tissue on respiratory function in rats with mid-cervical spinal cord injury. Embryonic day-14 rat FSC tissue was transplanted into a C4 spinal cord hemilesion cavity in adult male rats at 1 week postinjury...
January 17, 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/28097054/hydrogel-scaffolds-promote-neural-gene-expression-and-structural-reorganization-in-human-astrocyte-cultures
#14
V Bleu Knight, Elba E Serrano
Biomaterial scaffolds have the potential to enhance neuronal development and regeneration. Understanding the genetic responses of astrocytes and neurons to biomaterials could facilitate the development of synthetic environments that enable the specification of neural tissue organization with engineered scaffolds. In this study, we used high throughput transcriptomic and imaging methods to determine the impact of a hydrogel, PuraMatrix™, on human glial cells in vitro. Parallel studies were undertaken with cells grown in a monolayer environment on tissue culture polystyrene...
2017: PeerJ
https://www.readbyqxmd.com/read/28096339/loss-of-astrocyte-cholesterol-synthesis-disrupts-neuronal-function-and-alters-whole-body-metabolism
#15
Heather A Ferris, Rachel J Perry, Gabriela V Moreira, Gerald I Shulman, Jay D Horton, C Ronald Kahn
Cholesterol is important for normal brain function. The brain synthesizes its own cholesterol, presumably in astrocytes. We have previously shown that diabetes results in decreased brain cholesterol synthesis by a reduction in sterol regulatory element-binding protein 2 (SREBP2)-regulated transcription. Here we show that coculture of control astrocytes with neurons enhances neurite outgrowth, and this is reduced with SREBP2 knockdown astrocytes. In vivo, mice with knockout of SREBP2 in astrocytes have impaired brain development and behavioral and motor defects...
January 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28095365/barreloid-borders-and-neuronal-activity-shape-panglial-gap-junction-coupled-networks-in-the-mouse-thalamus
#16
Lena Claus, Camille Philippot, Stephanie Griemsmann, Aline Timmermann, Ronald Jabs, Christian Henneberger, Helmut Kettenmann, Christian Steinhäuser
The ventral posterior nucleus of the thalamus plays an important role in somatosensory information processing. It contains elongated cellular domains called barreloids, which are the structural basis for the somatotopic organization of vibrissae representation. So far, the organization of glial networks in these barreloid structures and its modulation by neuronal activity has not been studied. We have developed a method to visualize thalamic barreloid fields in acute slices. Combining electrophysiology, immunohistochemistry, and electroporation in transgenic mice with cell type-specific fluorescence labeling, we provide the first structure-function analyses of barreloidal glial gap junction networks...
November 24, 2016: Cerebral Cortex
https://www.readbyqxmd.com/read/28095299/african-and-asian-zika-virus-strains-differentially-induce-early-antiviral-responses-in-primary-human-astrocytes
#17
Rodolphe Hamel, Pauline Ferraris, Sineewanlaya Wichit, Fodé Diop, Loïc Talignani, Julien Pompon, Déborah Garcia, Florian Liegeois, Amadou A Sall, Hans Yssel, Dorothée Missé
ZIKA virus (ZIKV) is a newly emerging arbovirus. Since its discovery 60years ago in Uganda, it has spread throughout the Pacific, Latin America and the Caribbean, emphasizing the capacity of ZIKV to spread to non-endemic regions worldwide. Although infection with ZIKV often leads to mild disease, its recent emergence in the Americas has coincided with an increase in adults developing Guillain-Barré syndrome and neurological complications in new-borns, such as congenital microcephaly. Many questions remain unanswered regarding the complications caused by different primary isolates of ZIKV...
January 14, 2017: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/28093709/molecular-genetic-and-epigenetic-basis-of-multiple-sclerosis
#18
Zohreh Hojati
Multiple Sclerosis (MS) is a chronic immune-mediated disease of spinal cord and brain. The initial event in MS occurs when activated CD4(+) T cells in periphery exacerbates immune responses by stimulating immune cells such as B cells, CD8(+) cells, mast cells, granulocytes and monocytes. These proinflammatory cells pass blood brain barrier by secreting proinflammatory cytokines including TNF-α and INF-γ which activate adhesion factors. APCs (antigen-presenting cells) reactivate CD4(+) T cells after infiltrating the CNS and CD4(+) T cells produce cytokines and chemokines...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28093569/translational-evaluation-of-translocator-protein-as-a-marker-of-neuroinflammation-in-schizophrenia
#19
T Notter, J M Coughlin, T Gschwind, U Weber-Stadlbauer, Y Wang, M Kassiou, A C Vernon, D Benke, M G Pomper, A Sawa, U Meyer
Positron emission tomography (PET) imaging with radiotracers that target translocator protein 18 kDa (TSPO) has become a popular approach to assess putative neuroinflammatory processes and associated microglia activation in psychotic illnesses. It remains unclear, however, whether TSPO imaging can accurately capture low-grade inflammatory processes such as those present in schizophrenia and related disorders. Therefore, we evaluated the validity of TSPO as a disease-relevant marker of inflammation using a translational approach, which combined neurodevelopmental and neurodegenerative mouse models with PET imaging in patients with recent-onset schizophrenia and matched controls...
January 17, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28093548/astrocytic-control-of-synaptic-function
#20
REVIEW
Thomas Papouin, Jaclyn Dunphy, Michaela Tolman, Jeannine C Foley, Philip G Haydon
Astrocytes intimately interact with synapses, both morphologically and, as evidenced in the past 20 years, at the functional level. Ultrathin astrocytic processes contact and sometimes enwrap the synaptic elements, sense synaptic transmission and shape or alter the synaptic signal by releasing signalling molecules. Yet, the consequences of such interactions in terms of information processing in the brain remain very elusive. This is largely due to two major constraints: (i) the exquisitely complex, dynamic and ultrathin nature of distal astrocytic processes that renders their investigation highly challenging and (ii) our lack of understanding of how information is encoded by local and global fluctuations of intracellular calcium concentrations in astrocytes...
March 5, 2017: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
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