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https://www.readbyqxmd.com/read/28346104/bioengineered-3d-glial-cell-culture-systems-and-applications-for-neurodegeneration-and-neuroinflammation
#1
P Marc D Watson, Edel Kavanagh, Gary Allenby, Matthew Vassey
Neurodegeneration and neuroinflammation are key features in a range of chronic central nervous system (CNS) diseases such as Alzheimer's and Parkinson's disease, as well as acute conditions like stroke and traumatic brain injury, for which there remains significant unmet clinical need. It is now well recognized that current cell culture methodologies are limited in their ability to recapitulate the cellular environment that is present in vivo, and there is a growing body of evidence to show that three-dimensional (3D) culture systems represent a more physiologically accurate model than traditional two-dimensional (2D) cultures...
February 1, 2017: SLAS Discov
https://www.readbyqxmd.com/read/28345587/derivation-of-functional-human-astrocytes-from-cerebral-organoids
#2
Rômulo Sperduto Dezonne, Rafaela Costa Sartore, Juliana Minardi Nascimento, Verônica M Saia-Cereda, Luciana Ferreira Romão, Soniza Vieira Alves-Leon, Jorge Marcondes de Souza, Daniel Martins-de-Souza, Stevens Kastrup Rehen, Flávia Carvalho Alcantara Gomes
Astrocytes play a critical role in the development and homeostasis of the central nervous system (CNS). Astrocyte dysfunction results in several neurological and degenerative diseases. However, a major challenge to our understanding of astrocyte physiology and pathology is the restriction of studies to animal models, human post-mortem brain tissues, or samples obtained from invasive surgical procedures. Here, we report a protocol to generate human functional astrocytes from cerebral organoids derived from human pluripotent stem cells...
March 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28344867/cd4-and-cd8-t-cells-are-both-needed-to-induce-paraneoplastic-neurological-disease-in-a-mouse-model
#3
Christina Gebauer, Béatrice Pignolet, Lidia Yshii, Emilie Mauré, Jan Bauer, Roland Liblau
Paraneoplastic neurological disorders (PNDs) are rare human autoimmune diseases that mostly affect the central nervous system (CNS). They are triggered by an efficient immune response against a neural self-antigen that is ectopically expressed in neoplastic tumors. Due to this shared antigenic expression, the immune system reacts not only to tumor cells but also to neural cells resulting in neurological damage. Growing data point to a major role of cell-mediated immunity in PNDs associated to autoantibodies against intracellular proteins...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28344151/enhancing-oligodendrocyte-differentiation-by-transient-transcription-activation-via-dna-nanoparticle-mediated-transfection
#4
Xiaowei Li, Stephany Y Tzeng, Camila Gadens Zamboni, Vassilis E Koliatsos, Guo-Li Ming, Jordan J Green, Hai-Quan Mao
Current approaches to derive oligodendrocytes from human pluripotent stem cells (hPSCs) need extended exposure of hPSCs to growth factors and small molecules, which limits their clinical application because of the lengthy culture time required and low generation efficiency of myelinating oligodendrocytes. Compared to extrinsic growth factors and molecules, oligodendrocyte differentiation and maturation can be more effectively modulated by regulation of the cell transcription network. In the developing central nervous system (CNS), two basic helix-loop-helix transcription factors, Olig1 and Olig2, are decisive in oligodendrocyte differentiation and maturation...
March 23, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28342942/the-nature-of-early-astroglial-protection-fast-activation-and-signaling
#5
REVIEW
Julianna Kardos, László Héja, Katalin Jemnitz, Richárd Kovács, Miklós Palkovits
Our present review is focusing on the uniqueness of balanced astroglial signaling. The balance of excitatory and inhibitory signaling within the CNS is mainly determined by sharp synaptic transients of excitatory glutamate (Glu) and inhibitory γ-aminobutyrate (GABA) acting on the sub-second timescale. Astroglia is involved in excitatory chemical transmission by taking up i) Glu through neurotransmitter-sodium transporters, ii) K(+) released due to presynaptic action potential generation, and iii) water keeping osmotic pressure...
March 22, 2017: Progress in Neurobiology
https://www.readbyqxmd.com/read/28342781/modulation-of-neuroinflammation-the-role-and-therapeutic-potential-of-transient-receptor-potential-vanilloid-1-in-neuro-immune-axis
#6
REVIEW
Wei-Lin Kong, Yuan-Yuan Peng, Bi-Wen Peng
Transient receptor potential vanilloid type 1 channel (TRPV1), as a ligand-gated non-selective cation channel, has recently been demonstrated to have wide expression in the neuro-immune axis, where its multiple functions occur through regulation of both neuronal and non-neuronal activities. Growing evidence has suggested that TRPV1 is functionally expressed in glial cells, especially in the microglia and astrocytes. Glial cells perform immunological functions in response to pathophysiological challenges through pro-inflammatory or anti-inflammatory cytokines and chemokines in which TRPV1 is involved...
March 22, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28341037/influenza-virus-infection-exacerbates-experimental-autoimmune-encephalomyelitis-disease-by-promoting-type-i-t-cells-infiltration-into-central-nervous-system
#7
Qingyun Chen, Yinping Liu, Aizhen Lu, Ke Ni, Zheng Xiang, Kun Wen, Wenwei Tu
Multiple sclerosis starts with increased migration of auto-reactive lymphocytes across the blood-brain barrier, resulting in persistent neurodegeneration. Clinical and epidemiological studies indicated upper respiratory viral infections are associated with clinical exacerbation of multiple sclerosis. However, so far there is no any direct evidence to support it. Using the experimental autoimmune encephalomyelitis mice as the model for multiple sclerosis, we demonstrated that mice experienced with influenza virus infection were unable to recover from experimental autoimmune encephalomyelitis with a long-term exacerbation...
February 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28340587/lymphocytes-have-a-role-in-protection-but-not-in-pathogenesis-during-la-crosse-virus-infection-in-mice
#8
Clayton W Winkler, Lara M Myers, Tyson A Woods, Aaron B Carmody, Katherine G Taylor, Karin E Peterson
BACKGROUND: La Crosse Virus (LACV) is a primary cause of pediatric viral encephalitis in the USA and can result in severe clinical outcomes. Almost all cases of LACV encephalitis occur in children 16 years or younger, indicating an age-related susceptibility. This susceptibility is recapitulated in a mouse model where weanling (3 weeks old or younger) mice are susceptible to LACV-induced disease, and adults (greater than 6 weeks) are resistant. Disease in mice and humans is associated with infiltrating leukocytes to the CNS...
March 24, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28339401/is-huntingtin-dispensable-in-the-adult-brain
#9
Jeh-Ping Liu, Scott O Zeitlin
Huntingtin (HTT) is an essential protein during early embryogenesis and the development of the central nervous system (CNS). Conditional knock-out of mouse Huntingtin (Htt) expression in the CNS beginning during neural development, as well as reducing Htt expression only during embryonic and early postnatal stages, results in neurodegeneration in the adult brain. These findings suggest that HTT is important for the development and/or maintenance of the CNS, but they do not address the question of whether HTT is required specifically in the adult CNS for its normal functions and/or homeostasis...
March 21, 2017: Journal of Huntington's Disease
https://www.readbyqxmd.com/read/28339319/intrathecal-magnetic-drug-targeting-for-localized-delivery-of-therapeutics-in-the-cns
#10
Indu Venugopal, Nazia Habib, Andreas Linninger
AIM: The challenge in treating neurological diseases is not lack of drug potency, but ineffective targeting techniques. We propose a technique called intrathecal magnetic drug targeting (IT-MDT), in which intrathecally injected magnetic nanoparticles (MNPs) are targeted to specific sites using external magnets. MATERIALS & METHODS: MRI and histology confirmed localization of MNPs via IT-MDT at target sites along the spine of Sprague-Dawley rats. RESULTS: MRI results confirmed greater MNP localization when the duration of magnet application was extended...
March 24, 2017: Nanomedicine
https://www.readbyqxmd.com/read/28338622/phosphodiesterase-inhibitors-as-a-therapeutic-approach-to-neuroprotection-and-repair
#11
REVIEW
Eric P Knott, Mazen Assi, Sudheendra N R Rao, Mousumi Ghosh, Damien D Pearse
A wide diversity of perturbations of the central nervous system (CNS) result in structural damage to the neuroarchitecture and cellular defects, which in turn are accompanied by neurological dysfunction and abortive endogenous neurorepair. Altering intracellular signaling pathways involved in inflammation and immune regulation, neural cell death, axon plasticity and remyelination has shown therapeutic benefit in experimental models of neurological disease and trauma. The second messengers, cyclic adenosine monophosphate (cyclic AMP) and cyclic guanosine monophosphate (cyclic GMP), are two such intracellular signaling targets, the elevation of which has produced beneficial cellular effects within a range of CNS pathologies...
March 24, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28338398/dexamethasone-suppresses-jmjd3-gene-activation-via-a-putative-negative-glucocorticoid-response-element-and-maintains-integrity-of-tight-junctions-in-brain-microvascular-endothelial-cells
#12
Wonho Na, Jee Y Shin, Jee Y Lee, Sangyun Jeong, Won-Sun Kim, Tae Y Yune, Bong-Gun Ju
The blood-brain barrier (BBB) exhibits a highly selective permeability to support the homeostasis of the central nervous system (CNS). The tight junctions in the BBB microvascular endothelial cells seal the paracellular space to prevent diffusion. Thus, disruption of tight junctions results in harmful effects in CNS diseases and injuries. It has recently been demonstrated that glucocorticoids have beneficial effects on maintaining tight junctions in both in vitro cell and in vivo animal models. In the present study, we found that dexamethasone suppresses the expression of JMJD3, a histone H3K27 demethylase, via the recruitment of glucocorticoid receptor α (GRα) and nuclear receptor co-repressor (N-CoR) to the negative glucocorticoid response element (nGRE) in the upstream region of JMJD3 gene in brain microvascular endothelial cells subjected to TNFα treatment...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28337888/decitabine-treatment-for-acute-myeloid-leukemia-relapse-after-allogeneic-hematopoietic-stem-cell-transplantation
#13
X L Liu, X Zhao, C Wang, S J Gao, Y H Tan
Therapeutic options for patients with relapse of acute myeloid leukemia (AML) after allo-SCT are limited. Here, we present a case of a 49-year female with AML who underwent myeloablative allo-SCT from a matched sibling donor. Seven months after transplantation she developed cGVHD and suffered from extramedullary plus concurrent medullary relapse. The presence of CNS extramedullary disease is unique. Our patient was treated with decetabine. After one cycle the patient achieved complete remission and full donor chimerism without severe side effects or the occurrence of GVHD...
January 2017: Journal of Biological Regulators and Homeostatic Agents
https://www.readbyqxmd.com/read/28337644/cns-demyelination-with-tnf-%C3%AE-blockers
#14
REVIEW
Elissavet Kemanetzoglou, Elisabeth Andreadou
Tumor necrosis factor-α (TNF-α) blockers are a popular therapeutic choice in a number of inflammatory diseases. Thus far, five TNF- α blockers have been approved for clinical use (etanercept, infliximab, adalimumab, golimumab. and certolizumab). Despite being considered relatively safe, serious side effects associated with immune suppression have been reported, including central and peripheral nervous system (CNS) demyelinating disorders. It is still elusive whether these events are mere coincidence or a side effect of anti-TNF-α use...
April 2017: Current Neurology and Neuroscience Reports
https://www.readbyqxmd.com/read/28337172/bone-marrow-derived-cell-accumulation-in-the-spinal-cord-is-independent-of-peripheral-mobilization-in-a-mouse-model-of-amyotrophic-lateral-sclerosis
#15
Kyle Peake, John Manning, Coral-Ann Lewis, Kevin Tran, Fabio Rossi, Charles Krieger
Bone marrow-derived cells (BMDCs) are capable of migrating across the blood-brain barrier (BBB) and accumulating in the central nervous system (CNS) when transplanted into recipients conditioned with whole-body irradiation or chemotherapy. We used the chemotherapeutic agents busulfan and treosulfan to condition recipient mice for transplantation with bone marrow (BM) cells isolated from donor mice ubiquitously expressing green fluorescent protein. We attempted to increase the accumulation of BMDCs in the CNS by mobilization of BMDCs using either, or both, granulocyte colony-stimulating factor (GCSF) or plerixafor (AMD3100)...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28337127/nlrp3-inflammasome-in-neurological-diseases-from-functions-to-therapies
#16
REVIEW
Limin Song, Lei Pei, Shanglong Yao, Yan Wu, You Shang
Neuroinflammation has been identified as a causative factor of multiple neurological diseases. The nucleotide-binding oligomerization domain-, leucine-rich repeat- and pyrin domain-containing 3 (NLRP3) inflammasome, a subcellular multiprotein complex that is abundantly expressed in the central nervous system (CNS), can sense and be activated by a wide range of exogenous and endogenous stimuli such as microbes, aggregated and misfolded proteins, and adenosine triphosphate, which results in activation of caspase-1...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28337124/interleukin-4-protects-dopaminergic-neurons-in-vitro-but-is-dispensable-for-mptp-induced-neurodegeneration-in-vivo
#17
Laura Hühner, Jennifer Rilka, Ralf Gilsbach, Xiaolai Zhou, Venissa Machado, Björn Spittau
Microglia are involved in physiological as well as neuropathological processes in the central nervous system (CNS). Their functional states are often referred to as M1-like and M2-like activation, and are believed to contribute to neuroinflammation-mediated neurodegeneration or neuroprotection, respectively. Parkinson's disease (PD) is one the most common neurodegenerative disease and is characterized by the progressive loss of midbrain dopaminergic (mDA) neurons in the substantia nigra resulting in bradykinesia, tremor, and rigidity...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28336359/enrichment-and-isolation-of-neurons-from-adult-mouse-brain-for-ex-vivo-analysis
#18
Sabina Berl, Khalad Karram, Anja Scheller, Melanie Jungblut, Frank Kirchhoff, Ari Waisman
BACKGROUND: Isolation of neurons from the adult mouse CNS is important in order to study their gene expression during development or the course of different diseases. NEW METHODS: Here we present two different methods for the enrichment or isolation of neurons from adult mouse CNS. These methods: are either based on flow cytometry sorting of eYFP expressing neurons, or by depletion of non-neuronal cells by sorting with magnetic-beads. RESULTS: Enrichment by FACS sorting of eYFP positive neurons results in a population of 62...
March 20, 2017: Journal of Neuroscience Methods
https://www.readbyqxmd.com/read/28335421/pamam-dendrimers-cross-the-blood-brain-barrier-when-administered-through-the-carotid-artery-in-c57bl-6j-mice
#19
Bhairavi Srinageshwar, Sarah Peruzzaro, Melissa Andrews, Kayla Johnson, Allison Hietpas, Brittany Clark, Crystal McGuire, Eric Petersen, Jordyn Kippe, Andrew Stewart, Olivia Lossia, Abeer Al-Gharaibeh, Aaron Antcliff, Rebecca Culver, Douglas Swanson, Gary Dunbar, Ajit Sharma, Julien Rossignol
Drug delivery into the central nervous system (CNS) is challenging due to the blood-brain barrier (BBB) and drug delivery into the brain overcoming the BBB can be achieved using nanoparticles such as dendrimers. The conventional cationic dendrimers used are highly toxic. Therefore, the present study investigates the role of novel mixed surface dendrimers, which have potentially less toxicity and can cross the BBB when administered through the carotid artery in mice. In vitro experiments investigated the uptake of amine dendrimers (G1-NH₂ and G4-NH₂) and novel dendrimers (G1-90/10 and G4-90/10) by primary cortical cultures...
March 14, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28334745/disease-correction-by-aav-mediated-gene-therapy-in-a-new-mouse-model-of-mucopolysaccharidosis-type-iiid
#20
Carles Roca, Sandra Motas, Sara Marcó, Albert Ribera, Víctor Sánchez, Xavier Sánchez, Joan Bertolin, Xavier León, Jennifer Pérez, Miguel Garcia, Pilar Villacampa, Jesús Ruberte, Anna Pujol, Virginia Haurigot, Fatima Bosch
Gene therapy is a promising therapeutic alternative for Lysosomal Storage Disorders (LSD), as it is not necessary to correct the genetic defect in all cells of an organ to achieve therapeutically significant levels of enzyme in body fluids, from which non-transduced cells can uptake the protein correcting their enzymatic deficiency. Animal models are instrumental in the development of new treatments for LSD. Here we report the generation of the first mouse model of the LSD Muccopolysaccharidosis Type IIID (MPSIIID), also known as Sanfilippo syndrome type D...
February 17, 2017: Human Molecular Genetics
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