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https://www.readbyqxmd.com/read/28546318/an-environment-dependent-transcriptional-network-specifies-human-microglia-identity
#1
David Gosselin, Dylan Skola, Nicole G Coufal, Inge R Holtman, Johannes C M Schlachetzki, Eniko Sajti, Baptiste N Jaeger, Carolyn O'Connor, Conor Fitzpatrick, Martina P Pasillas, Monique Pena, Amy Adair, David G Gonda, Michael L Levy, Richard M Ransohoff, Fred H Gage, Christopher K Glass
Microglia play essential roles in central nervous system (CNS) homeostasis and influence diverse aspects of neuronal function. However, the transcriptional mechanisms that specify human microglia phenotypes are largely unknown. We examined the transcriptomes and epigenetic landscapes of human microglia isolated from surgically resected brain tissue ex vivo and following transition to an in vitro environment. Transfer to a tissue culture environment results in rapid and extensive downregulation of microglia-specific genes that are induced in primitive mouse macrophages following migration into the fetal brain...
May 25, 2017: Science
https://www.readbyqxmd.com/read/28544974/cetuximab-modified-collagen-scaffold-directs-neurogenesis-of-injury-activated-endogenous-neural-stem-cells-for-acute-spinal-cord-injury-repair
#2
Xing Li, Yannan Zhao, Shixiang Cheng, Sufang Han, Muya Shu, Bing Chen, Xuyi Chen, Fengwu Tang, Nuo Wang, Yue Tu, Bin Wang, Zhifeng Xiao, Sai Zhang, Jianwu Dai
Studies have shown that endogenous neural stem cells (NSCs) activated by spinal cord injury (SCI) primarily generate astrocytes to form glial scar. The NSCs do not differentiate into neurons because of the adverse microenvironment. In this study, we defined the activation timeline of endogenous NSCs in rats with severe SCI. These injury-activated NSCs then migrated into the lesion site. Cetuximab, an EGFR signaling antagonist, significantly increased neurogenesis in the lesion site. Meanwhile, implanting cetuximab modified linear ordered collagen scaffolds (LOCS) into SCI lesion sites in dogs resulted in neuronal regeneration, including neuronal differentiation, maturation, myelination, and synapse formation...
May 18, 2017: Biomaterials
https://www.readbyqxmd.com/read/28544655/3d-bioprinting-human-induced-pluripotent-stem-cell-constructs-for-in-situ-cell-proliferation-and-successive-multilineage-differentiation
#3
Qi Gu, Eva Tomaskovic-Crook, Gordon G Wallace, Jeremy M Crook
The ability to create 3D tissues from induced pluripotent stem cells (iPSCs) is poised to revolutionize stem cell research and regenerative medicine, including individualized, patient-specific stem cell-based treatments. There are, however, few examples of tissue engineering using iPSCs. Their culture and differentiation is predominantly planar for monolayer cell support or induction of self-organizing embryoids (EBs) and organoids. Bioprinting iPSCs with advanced biomaterials promises to augment efforts to develop 3D tissues, ideally comprising direct-write printing of cells for encapsulation, proliferation, and differentiation...
May 24, 2017: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/28543993/genetic-background-of-hirschsprung-disease-a-bridge-between-basic-science-and-clinical-application
#4
Afsane Bahrami, Marjan Joodi, Mehrdad Ahmadi, Mina Maftouh, Seyed Mahdi Hassanian, Gordon A Ferns, Amir Avan
Hirschsprung's disease (HSCR) is a congenital disorder, defined by partial or complete loss of the neuronal ganglion cells in the intestinal tract, which is caused by the failure of neural crest cells to migrate completely during intestinal development during fetal life. HSCR has a multifactorial etiology, and genetic factors play a key role in its pathogenesis; these include mutations within several gene loci. These have been identified by screening candidate genes, or by conducting genome wide association (GWAS) studies...
May 19, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28542923/the-polysialic-acid-mimetics-idarubicin-and-irinotecan-stimulate-neuronal-survival-and-neurite-outgrowth-and-signal-via-protein-kinase-c
#5
Gabriele Loers, Steven Astafiev, Yuliya Hapiak, Vedangana Saini, Bibhudatta Mishra, Sheraz Gul, Gurcharan Kaur, Melitta Schachner, Thomas Theis
Polysialic acid (PSA) is a large, negatively charged, linear homopolymer of alpha2-8-linked sialic acid residues. It is generated by two polysialyltransferases and attached to N- and/or O-linked glycans, and its main carrier is the neural cell adhesion molecule NCAM. PSA controls the development and regeneration of the nervous system by enhancing cell migration, axon pathfinding, synaptic targeting, synaptic plasticity, by regulating the differentiation of progenitor cells and by modulating cell-cell and cell-matrix adhesions...
May 24, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28542676/detailed-clinical-phenotype-and-molecular-genetic-findings-in-cln3-associated-isolated-retinal-degeneration
#6
Cristy A Ku, Sarah Hull, Gavin Arno, Ajoy Vincent, Keren Carss, Robert Kayton, Douglas Weeks, Glenn W Anderson, Ryan Geraets, Camille Parker, David A Pearce, Michel Michaelides, Robert E MacLaren, Anthony G Robson, Graham E Holder, Elise Heon, F Lucy Raymond, Anthony T Moore, Andrew R Webster, Mark E Pennesi
Importance: Mutations in genes traditionally associated with syndromic retinal disease are increasingly found to cause nonsyndromic inherited retinal degenerations. Mutations in CLN3 are classically associated with juvenile neuronal ceroid lipofuscinosis, a rare neurodegenerative disease with early retinal degeneration and progressive neurologic deterioration, but have recently also been identified in patients with nonsyndromic inherited retinal degenerations. To our knowledge, detailed clinical characterization of such cases has yet to be reported...
May 25, 2017: JAMA Ophthalmology
https://www.readbyqxmd.com/read/28542541/varicella-zoster-virus-glycoprotein-c-increases-chemokine-mediated-leukocyte-migration
#7
Víctor González-Motos, Carina Jürgens, Birgit Ritter, Kai A Kropp, Verónica Durán, Olav Larsen, Anne Binz, Werner J D Ouwendijk, Tihana Lenac Rovis, Stipan Jonjic, Georges M G M Verjans, Beate Sodeik, Thomas Krey, Rudolf Bauerfeind, Thomas F Schulz, Benedikt B Kaufer, Ulrich Kalinke, Amanda E I Proudfoot, Mette M Rosenkilde, Abel Viejo-Borbolla
Varicella zoster virus (VZV) is a highly prevalent human pathogen that establishes latency in neurons of the peripheral nervous system. Primary infection causes varicella whereas reactivation results in zoster, which is often followed by chronic pain in adults. Following infection of epithelial cells in the respiratory tract, VZV spreads within the host by hijacking leukocytes, including T cells, in the tonsils and other regional lymph nodes, and modifying their activity. In spite of its importance in pathogenesis, the mechanism of dissemination remains poorly understood...
May 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28542414/the-intestinal-torc2-signaling-pathway-contributes-to-associative-learning-in-caenorhabditis-elegans
#8
Naoko Sakai, Hayao Ohno, Masahiro Tomioka, Yuichi Iino
Several types of associative learning are dependent upon the presence or absence of food, and are crucial for the survival of most animals. Target of rapamycin (TOR), a kinase which exists as a component of two complexes, TOR complex 1 (TORC1) and TOR complex 2 (TORC2), is known to act as a nutrient sensor in numerous organisms. However, the in vivo roles of TOR signaling in the nervous system remain largely unclear, partly because its multifunctionality and requirement for survival make it difficult to investigate...
2017: PloS One
https://www.readbyqxmd.com/read/28542170/human-mutations-in-integrator-complex-subunits-link-transcriptome-integrity-to-brain-development
#9
Renske Oegema, David Baillat, Rachel Schot, Leontine M van Unen, Alice Brooks, Sima Kheradmand Kia, A Jeannette M Hoogeboom, Zheng Xia, Wei Li, Matteo Cesaroni, Maarten H Lequin, Marjon van Slegtenhorst, William B Dobyns, Irenaeus F M de Coo, Frans W Verheijen, Andreas Kremer, Peter J van der Spek, Daphne Heijsman, Eric J Wagner, Maarten Fornerod, Grazia M S Mancini
Integrator is an RNA polymerase II (RNAPII)-associated complex that was recently identified to have a broad role in both RNA processing and transcription regulation. Importantly, its role in human development and disease is so far largely unexplored. Here, we provide evidence that biallelic Integrator Complex Subunit 1 (INTS1) and Subunit 8 (INTS8) gene mutations are associated with rare recessive human neurodevelopmental syndromes. Three unrelated individuals of Dutch ancestry showed the same homozygous truncating INTS1 mutation...
May 25, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28537554/pioneer-neurog1-expressing-cells-ingress-into-the-otic-epithelium-and-instruct-neuronal-specification
#10
Esteban Hoijman, Laura Fargas, Patrick Blader, Berta Alsina
Neural patterning involves regionalised cell specification. Recent studies indicate that cell dynamics play instrumental roles in neural pattern refinement and progression, but the impact of cell behaviour and morphogenesis on neural specification is not understood. Here we combine 4D analysis of cell behaviours with dynamic quantification of proneural expression to uncover the construction of the zebrafish otic neurogenic domain. We identify pioneer cells expressing neurog1 outside the otic primordium that migrate and ingress into the epithelialising placode to become the first otic neuronal progenitors...
May 24, 2017: ELife
https://www.readbyqxmd.com/read/28536635/the-regulatory-mechanisms-of-ng2-cspg4-expression
#11
REVIEW
Emmanuel Ampofo, Beate M Schmitt, Michael D Menger, Matthias W Laschke
Neuron-glial antigen 2 (NG2), also known as chondroitin sulphate proteoglycan 4 (CSPG4), is a surface type I transmembrane core proteoglycan that is crucially involved in cell survival, migration and angiogenesis. NG2 is frequently used as a marker for the identification and characterization of certain cell types, but little is known about the mechanisms regulating its expression. In this review, we provide evidence that the regulation of NG2 expression underlies inflammation and hypoxia and is mediated by methyltransferases, transcription factors, including Sp1, paired box (Pax) 3 and Egr-1, and the microRNA miR129-2...
2017: Cellular & Molecular Biology Letters
https://www.readbyqxmd.com/read/28536274/mapping-22q11-2-gene-dosage-effects-on-brain-morphometry
#12
Amy Lin, Christopher R K Ching, Ariana Vajdi, Daqiang Sun, Rachel K Jonas, Maria Jalbrzikowski, Leila Kushan-Wells, Laura Pacheco Hansen, Emma Krikorian, Boris Gutman, Deepika Dokoru, Gerhard Helleman, Paul M Thompson, Carrie E Bearden
Reciprocal chromosomal rearrangements at the 22q11.2 locus are associated with elevated risk of neurodevelopmental disorders. The 22q11.2 deletion confers the highest known genetic risk for schizophrenia, but a duplication in the same region is strongly associated with autism and is less common in schizophrenia cases than in the general population. Here we conducted the first study of 22q11.2 gene dosage effects on brain structure in a sample of 143 human subjects: 66 with 22q11.2 deletions (22q-del; 32 males), 21 with 22q11...
May 23, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28533745/characterization-of-induced-pluripotent-stem-cell-derived-human-serotonergic-neurons
#13
Lining Cao, Rui Hu, Ting Xu, Zhen-Ning Zhang, Weida Li, Jianfeng Lu
In the brain, the serotonergic neurons located in the raphe nucleus are the unique resource of the neurotransmitter serotonin, which plays a pivotal role in the regulation of brain development and functions. Dysfunction of the serotonin system is present in many psychiatric disorders. Lack of in vitro functional human model limits the understanding of human central serotonergic system and its related diseases and clinical applications. Previously, we have developed a method generating human serotonergic neurons from induced pluripotent stem cells (iPSCs)...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28530245/shifting-the-optimal-stiffness-for-cell-migration
#14
Benjamin L Bangasser, Ghaidan A Shamsan, Clarence E Chan, Kwaku N Opoku, Erkan Tüzel, Benjamin W Schlichtmann, Jesse A Kasim, Benjamin J Fuller, Brannon R McCullough, Steven S Rosenfeld, David J Odde
Cell migration, which is central to many biological processes including wound healing and cancer progression, is sensitive to environmental stiffness, and many cell types exhibit a stiffness optimum, at which migration is maximal. Here we present a cell migration simulator that predicts a stiffness optimum that can be shifted by altering the number of active molecular motors and clutches. This prediction is verified experimentally by comparing cell traction and F-actin retrograde flow for two cell types with differing amounts of active motors and clutches: embryonic chick forebrain neurons (ECFNs; optimum ∼1 kPa) and U251 glioma cells (optimum ∼100 kPa)...
May 22, 2017: Nature Communications
https://www.readbyqxmd.com/read/28528122/probdnf-inhibits-proliferation-migration-and-differentiation-of-mouse-neural-stem-cells
#15
Jia-Yi Li, Jia Liu, Nimshitha Pavathuparambil Abdul Manaph, Larisa Bobrovskaya, Xin-Fu Zhou
ProBDNF, a precursor of brain-derived neurotrophic factor (BDNF), is an important regulator of neurodegeneration, hippocampal long-term depression, and synaptic plasticity. ProBDNF and its receptors pan-neurotrophin receptor p75 (p75NTR), vps10p domain-containing receptor Sortilin and tropomyosin receptor kinase B (TrkB) are expressed in neuronal and glial cells. The role of proBDNF in regulation of neurogenesis is not fully defined. This study aims to uncover the function of proBDNF in regulating the differentiation, migration and proliferation of mouse neural stem cells (NSCs) in vitro...
May 17, 2017: Brain Research
https://www.readbyqxmd.com/read/28526411/jnj10181457-a-histamine-h3-receptor-inverse-agonist-regulates-in-vivo-microglial-functions-and-improves-depression-like-behaviours-in-mice
#16
Tomomitsu Iida, Takeo Yoshikawa, Anikó Kárpáti, Takuro Matsuzawa, Haruna Kitano, Asuka Mogi, Ryuichi Harada, Fumito Naganuma, Tadaho Nakamura, Kazuhiko Yanai
Brain histamine acts as a neurotransmitter and regulates various physiological functions, such as learning and memory, sleep-wake cycles, and appetite regulation. We have recently shown that histamine H3 receptor (H3R) is expressed in primary mouse microglia and has a strong influence on critical functions in microglia, including chemotaxis, phagocytosis, and cytokine secretion in vitro. However, the importance of H3R in microglial activity in vivo remains unknown. Here, we examined the effects of JNJ10181457 (JNJ), a selective and potent H3R inverse agonist, on microglial functions ex vivo and in vivo...
May 16, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28522884/profiles-of-periglomerular-cells-in-the-olfactory-bulb-of-prokineticin-type-2-receptor-deficient-mice
#17
Atsuko Kubo, Mitsugu Sujino, Koh-Hei Masumoto, Atsuko Fujioka, Toshio Terashima, Yasufumi Shigeyoshi, Mamoru Nagano
Both prokineticin receptor 2 (pkr2) and prokineticin 2 (pk2) gene-deficient mice have hypoplasia of the main olfactory bulb (MOB). This hypoplasia has been attributed to disruption of the glomerulus that is caused by loss of afferent projection from olfactory sensory neurons (OSN), and to the impaired migration of granule cells, a type of interneuron. In the present study, we examined whether migration of the second type of interneuron, periglomerular cells (PGC), is dependent on the pkr2 expression by observing the localization of distinct subpopulations of PGC: calretinin (CR)-, calbindin (CB)- and tyrosine hydroxylase (TH)-expressing neurons...
April 27, 2017: Acta Histochemica et Cytochemica
https://www.readbyqxmd.com/read/28522413/microglia-support-atf3-positive-neurons-following-hypoglossal-nerve-axotomy
#18
Tatsuhide Tanaka, Koichi Murakami, Yoshio Bando, Taichi Nomura, Ayami Isonishi, Shoko Morita-Takemura, Kouko Tatsumi, Akio Wanaka, Shigetaka Yoshida
Microglia are essential in developmental processes and maintenance of neuronal homeostasis. Experimental axotomy of motor neurons results in neurodegeneration, and microglia in motor nuclei become activated and migrate towards injured neurons. However, whether these activated microglia are protective or destructive to neurons remains controversial. In the present study, we transected the hypoglossal nerve in BALB/c mice, causing activating transcription factor 3 (ATF3) and growth associated protein 43 (GAP43) induction, and partial neuronal death...
May 15, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28517363/cleave-but-not-leave-astrotactin-proteins-in-development-and-disease
#19
REVIEW
Hao Chang
Over the years, animal studies have identified astrotactins as important membrane proteins for glial-guided neuronal migration during central nervous system development and hair follicle polarity control during skin development. Biochemical studies have revealed intramembrane proteolysis as an important feature of astrotactins. The two fragments of astrotactins remain linked together by a disulfide bond after the proteolytic cleavage. In humans, mutations in astrotactin genes have also been linked to a wide range of diseases, including several developmental brain disorders, neurodegenerative diseases and cancer...
May 18, 2017: IUBMB Life
https://www.readbyqxmd.com/read/28516224/psychiatric-behaviors-associated-with-cytoskeletal-defects-in-radial-neuronal-migration
#20
REVIEW
Toshifumi Fukuda, Shigeru Yanagi
Normal development of the cerebral cortex is an important process for higher brain functions, such as language, and cognitive and social functions. Psychiatric disorders, such as schizophrenia and autism, are thought to develop owing to various dysfunctions occurring during the development of the cerebral cortex. Radial neuronal migration in the embryonic cerebral cortex is a complex process, which is achieved by strict control of cytoskeletal dynamics, and impairments in this process are suggested to cause various psychiatric disorders...
May 17, 2017: Cellular and Molecular Life Sciences: CMLS
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