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https://www.readbyqxmd.com/read/29161339/astrocyte-specific-deletion-of-sox2-promotes-functional-recovery-after-traumatic-brain-injury
#1
Chunhai Chen, Xiaoling Zhong, Derek K Smith, Wenjiao Tai, Jianjing Yang, Yuhua Zou, Lei-Lei Wang, Jiahong Sun, Song Qin, Chun-Li Zhang
Injury to the adult brain induces activation of local astrocytes, which serves as a compensatory response that modulates tissue damage and recovery. However, the mechanism governing astrocyte activation during brain injury remains largely unknown. Here we provide in vivo evidence that SOX2, a transcription factor critical for stem cells and brain development, is also required for injury-induced activation of adult cortical astrocytes. Genome-wide chromatin immunoprecipitation-seq analysis of mouse cortical tissues reveals that SOX2 binds to regulatory regions of genes associated with signaling pathways that control glial cell activation, such as Nr2e1, Mmd2, Wnt7a, and Akt2...
November 17, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/29159704/neuroimmune-regulation-of-jc-virus-by-intracellular-and-extracellular-agnoprotein
#2
Michael Craigie, Stephanie Cicalese, Ilker Kudret Sariyer
JC virus (JCV) is a human polyomavirus and the etiologic agent of the demyelinating disease progressive multifocal leukoencephalopathy (PML). PML is observed in patients with underlying immunocompromising conditions, suggesting that neuro-immune interactions between peripheral immune cells and neuro-glia play an important role in controlling viral reactivation in the brain. There is little known about the immunobiology of JCV reactivation in glial cells and the role of immune, glial, and viral players in this regulation...
November 20, 2017: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
https://www.readbyqxmd.com/read/29158604/antiviral-cd8-t-cells-induce-zika-virus-associated-paralysis-in-mice
#3
Kellie A Jurado, Laura J Yockey, Patrick W Wong, Sarah Lee, Anita J Huttner, Akiko Iwasaki
Zika virus (ZIKV) is an emerging, mosquito-borne RNA virus. The rapid spread of ZIKV within the Americas has unveiled microcephaly (1) and Guillain-Barré syndrome (2,3) as ZIKV-associated neurological complications. Recent reports have also indicated other neurological manifestations to be associated with ZIKV, including myelitis (4) , meningoencephalitis (5) and fatal encephalitis (6) . Here, we investigate the neuropathogenesis of ZIKV infection in type I interferon receptor IFNAR knockout (Ifnar1 (-/-) ) mice, an infection model that exhibits high viral burden within the central nervous system...
November 20, 2017: Nature Microbiology
https://www.readbyqxmd.com/read/29158308/glioblastoma-multiforme-derived-extracellular-vesicles-drive-normal-astrocytes-towards-a-tumour-enhancing-phenotype
#4
Soliman Oushy, Justin E Hellwinkel, Mary Wang, Ger J Nguyen, Dicle Gunaydin, Tessa A Harland, Thomas J Anchordoquy, Michael W Graner
Glioblastoma multiforme (GBM) is a devastating tumour with abysmal prognoses. We desperately need novel approaches to understand GBM biology and therapeutic vulnerabilities. Extracellular vesicles (EVs) are membrane-enclosed nanospheres released locally and systemically by all cells, including tumours, with tremendous potential for intercellular communication. Tumour EVs manipulate their local environments as well as distal targets; EVs may be a mechanism for tumourigenesis in the recurrent GBM setting. We hypothesized that GBM EVs drive molecular changes in normal human astrocytes (NHAs), yielding phenotypically tumour-promoting, or even tumourigenic, entities...
January 5, 2018: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/29157807/a-comparative-proteomic-study-of-secretomes-in-kaempferitrin-treated-ctx-tna2-astrocytic-cells
#5
Wei-Chi Ku, Yi-Ling Chang, Sheng-Fa Wu, Hui-Nung Shih, Yew-Min Tzeng, Hui-Ru Kuo, Kai-Ming Chang, Dinesh Chandra Agrawal, Bing-Lan Liu, Chin-An Chang, Siendong Huang, Meng-Jen Lee
ETHNOPHARMACOLOGICAL RELEVANCE: Kaempferitrin is extracted in significantly high quantities from the leaves of Cinnamomum osmophloeum (C.O) and Bauhinia forficata, and are used as an antidiabetic herbal remedy in China and Brazil. Commercial product using dry Cinnamomum osmophloeum leaves has been sold locally in Taiwan. Oral administration of kaempferitrin reduced blood sugar in diabetic rats. AIM OF THE STUDY: Though previously demonstrated to activate the classical insulin signaling pathways, a mechanism for kaempferitrin is still not fully understood...
December 1, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/29157673/circulating-micrornas-as-biomarkers-for-pediatric-astrocytomas
#6
Javier Enrique López-Aguilar, Miguel A Velázquez-Flores, Luis A Simón-Martínez, Richard Ávila-Miranda, Marco A Rodríguez-Florido, Ruth Ruiz-Esparza Garrido
BACKGROUND AND AIMS: Since MicroRNAs (miRNAs) are potent regulators of gene expression, their expression and function alterations are associated with different types of cancer, including pediatric astrocytoma. Since the secretion of miRNAs by tumors into corporal fluids has made it possible to identify biomarkers in cancer, their deter mination in pediatric astrocytoma is vital. In order to gain insight into the mechanisms controlled by miRNAs in these neoplasms, we tested the expression of miRNAs 130a, 145, 335, 1303, and let-7g-3p by qPCR in tumors and blood serum from pediatric patients with astrocytoma...
May 2017: Archives of Medical Research
https://www.readbyqxmd.com/read/29156730/generation-of-patient-specific-human-neural-stem-cells-from-niemann-pick-disease-type-c-patient-derived-fibroblasts
#7
Eun-Ah Sung, Kyung-Rok Yu, Ji-Hee Shin, Yoojin Seo, Hyung-Sik Kim, Myung Guen Koog, Insung Kang, Jae-Jun Kim, Byung-Chul Lee, Tae-Hoon Shin, Jin Young Lee, Seunghee Lee, Tae-Wook Kang, Soon Won Choi, Kyung-Sun Kang
Niemann-Pick disease type C (NPC) is a neurodegenerative and lysosomal lipid storage disorder, characterized by the abnormal accumulation of unesterified cholesterol and glycolipids, which is caused by mutations in the NPC1 genes. Here, we report the generation of human induced neural stem cells from NPC patient-derived fibroblasts (NPC-iNSCs) using only two reprogramming factors SOX2 and HMGA2 without going through the pluripotent state. NPC-iNSCs were stably expandable and differentiated into neurons, astrocytes, and oligodendrocytes...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29155887/effects-of-an-a%C3%AE-antibody-fragment-on-a%C3%AE-aggregation-and-astrocytic-uptake-are-modulated-by-apolipoprotein-e-and-j-mimetic-peptides
#8
Laia Montoliu-Gaya, Sandra D Mulder, Robert Veerhuis, Sandra Villegas
Aβ-Immunotherapy has long been studied in the treatment of Alzheimer's disease (AD), but not how other molecules involved in the disease can affect antibody performance. We previously designed an antibody fragment, scFv-h3D6, and showed that it precludes Aβ-induced cytotoxicity by withdrawing Aβ oligomers from the amyloid pathway towards a non-toxic, worm-like pathway. ScFv-h3D6 was effective at the behavioral, cellular, and molecular levels in the 3xTg-AD mouse model. Because scFv-h3D6 treatment restored apolipoprotein E (apoE) and J (apoJ) concentrations to non-pathological values, and Aβ internalization by glial cells was found to be decreased in the presence of these apolipoproteins, we now aimed to test the influence of scFv-h3D6 on Aβ aggregation and cellular uptake by primary human astrocytes in the presence of therapeutic apoE and apoJ mimetic peptides (MPs)...
2017: PloS One
https://www.readbyqxmd.com/read/29155711/monitoring-astrocyte-reactivity-and-proliferation-in-vitro-under-ischemic-like-conditions
#9
Yancy Ferrer-Acosta, Maxine N Gonzalez-Vega, David E Rivera-Aponte, Solianne M Martinez-Jimenez, Antonio H Martins
Ischemic stroke is a complex brain injury caused by a thrombus or embolus obstructing blood flow to parts of the brain. This leads to deprivation of oxygen and glucose, which causes energy failure and neuronal death. After an ischemic stroke insult, astrocytes become reactive and proliferate around the injury site as it develops. Under this scenario, it is difficult to study the specific contribution of astrocytes to the brain region exposed to ischemia. Therefore, this article introduces a methodology to study primary astrocyte reactivity and proliferation under an in vitro model of an ischemia-like environment, called oxygen glucose deprivation (OGD)...
October 21, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29155394/label-free-and-dynamic-monitoring-of-cytotoxicity-to-the-blood-brain-barrier-cells-treated-with-nanometre-copper-oxide
#10
Duan Lian, Zhang Chonghua, Gu Wen, Zhang Hongwei, Bai Xuetao
A cytotoxicity study was conducted with a primary culture of the nervous system cells, including brain microvascular endothelial cells (BMECs) and astrocytes, which are important components of the blood-brain barrier. The real-time cell analysis (RTCA) was used to determine the cytotoxicity of copper-oxide nanoparticles (CuO NPs). The IC50 values of CuO NPs in astrocytes and BMECs were determined by the RTCA at different exposure times and were used as base values for further research. DNA damage after exposure to CuO NPs for 3 and 24 h was assessed using comet assay at the IC50 obtained from RTCA...
December 2017: IET Nanobiotechnology
https://www.readbyqxmd.com/read/29155265/neuroanatomical-distribution-and-function-of-the-vasopressin-v1b-receptor-in-the-rat-brain-deciphered-using-specific-fluorescent-ligands
#11
Maithé Corbani, Rafik Marir, Miguel Trueba, Magda Chafai, Anne Vincent, Amélie M Borie, Michel G Desarménien, Yoichi Ueta, Csaba Tomboly, Aleksandra Olma, Maurice Manning, Gilles Guillon
It is now accepted that vasopressin, through V1A/V1B receptors, centrally regulates cognitive functions such as memory, affiliation, stress, fear and depression. However, the respective roles of these receptor isoforms and their contribution to stress-related pathologies remain uncertain. The development of new therapeutic treatments requires a precise knowledge of the distribution of these receptors within the brain, which has been so far hampered by the lack of selective V1B markers. In the present study, we have determined the pharmacological properties of three new potent rat V1B fluorescent ligands and demonstrated that they constitute valuable tools for simultaneous visualization and activation of native V1B receptors in living rat brain tissue...
November 16, 2017: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/29154923/dissociation-of-blood-brain-barrier-disruption-and-disease-manifestation-in-an-aquaporin-4-deficient-mouse-model-of-amyotrophic-lateral-sclerosis
#12
Saori Watanabe-Matsumoto, Yasuhiro Moriwaki, Takashi Okuda, Shinji Ohara, Koji Yamanaka, Yoichiro Abe, Masato Yasui, Hidemi Misawa
Aquaporin-4 (AQP4) is abundantly expressed in the central nervous system and is involved in the water balance in the cellular environment. Previous studies have reported that AQP4 expression is upregulated in rat models of amyotrophic lateral sclerosis (ALS), a fatal disease that affects motor neurons in the brain and spinal cord. In this study, we report that astrocytic AQP4 overexpression is evident during the course of disease in the spinal cord of an ALS mouse model, as well as in tissue from patients with ALS...
November 15, 2017: Neuroscience Research
https://www.readbyqxmd.com/read/29154837/neuroprotective-effect-of-an-nrf2-are-activator-identified-from-a-chemical-library-on-dopaminergic-neurons
#13
Yasuhiko Izumi, Harue Kataoka, Yuri Inose, Akinori Akaike, Yutaka Koyama, Toshiaki Kume
The nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway, which induces the production of antioxidant enzymes, is a possible therapeutic target for treating diseases related to oxidative stress. Nrf2 activators often exhibit cytotoxicity due to nonspecific electrophilic reactions with thiol groups. We screened a chemical library to explore Nrf2 activators with a wide safety margin. In at least in vitro experiments, TPNA10168, identified from the library, showed a higher efficacy in Nrf2 activation and a lower cytotoxicity than sulforaphane, a well-known Nrf2 activator...
November 14, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29154783/involvement-of-monocarboxylate-transporter-1-slc16a1-in-the-uptake-of-l-lactate-in-human-astrocytes
#14
Masaya Ideno, Masaki Kobayashi, Shotaro Sasaki, Yuya Futagi, Katsuya Narumi, Ayako Furugen, Ken Iseki
PURPOSE: Astrocytes, the most abundant glial cells in the central nervous system (CNS), help neurons survive Monocarboxylate transporters (MCTs) are reported to transport l-lactate, which is important for CNS physiology and cognitive function. However, it remains unclear which MCT isoform is functionally expressed by human astrocytes. The aim of this study was to establish the contribution of each MCT isoform to l-lactate transport in human astrocytes. METHODS: The function of l-lactate transport was studied using NHA cells as a human astrocyte model and radiolabeled l-lactate...
November 14, 2017: Life Sciences
https://www.readbyqxmd.com/read/29154375/glial-choristoma-of-the-ventral-part-of-the-tongue-first-report-in-an-elderly-patient
#15
M Nicola, F Ferrario, P Collini, M Onorati, M M Albertoni, F Di Nuovo
INTRODUCTION: The aims of this report are to illustrate the first case of glial and adipose tissue choristoma at the ventral part of the tongue in an elderly patient, to discuss the possible differential diagnoses and to speculate about its pathogenesis. CASE REPORT: A 65-year-old female was admitted to our hospital with a swelling at the base of the tongue. MRI revealed an oval lesion with indistinct borders without contrast enhancement. The patient underwent surgical complete excision and grossly, the specimen consisted of a gray-white mass measuring 25 mm in its great diameter...
September 2017: Pathologica
https://www.readbyqxmd.com/read/29154284/palmitoylethanolamide-blunts-amyloid-%C3%AE-42-induced-astrocyte-activation-and-improves-neuronal-survival-in-primary-mouse-cortical-astrocyte-neuron-co-cultures
#16
Sarah Beggiato, Andrea Celeste Borelli, Luca Ferraro, Sergio Tanganelli, Tiziana Antonelli, Maria Cristina Tomasini
BACKGROUND: Based on the pivotal role of astrocytes in brain homeostasis and the strong metabolic cooperation existing between neurons and astrocytes, it has been suggested that astrocytic dysfunctions might cause and/or contribute to neuroinflammation and neurodegenerative processes. Therapeutic approaches aimed at both neuroprotection and neuroinflammation reduction may prove particularly effective in slowing the progression of these diseases. The endogenous lipid mediator palmitoylethanolamide (PEA) displayed neuroprotective and anti(neuro)inflammatory properties, and demonstrated interesting potential as a novel treatment for Alzheimer's disease...
November 17, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29154076/multiple-intracerebroventricular-injections-of-human-umbilical-cord-mesenchymal-stem-cells-delay-motor-neurons-loss-but-not-disease-progression-of-sod1g93a-mice
#17
Francesca Sironi, Antonio Vallarola, Martina Bruna Violatto, Laura Talamini, Mattia Freschi, Roberta De Gioia, Chiara Capelli, Azzurra Agostini, Davide Moscatelli, Massimo Tortarolo, Paolo Bigini, Martino Introna, Caterina Bendotti
Stem cell therapy is considered a promising approach in the treatment of amyotrophic lateral sclerosis (ALS) and mesenchymal stem cells (MSCs) seem to be the most effective in ALS animal models. The umbilical cord (UC) is a source of highly proliferating fetal MSCs, more easily collectable than other MSCs. Recently we demonstrated that human (h) UC-MSCs, double labeled with fluorescent nanoparticles and Hoechst-33258 and transplanted intracerebroventricularly (ICV) into SOD1G93A transgenic mice, partially migrated into the spinal cord after a single injection...
November 10, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/29154037/sex-and-age-specific-modulation-of-brain-gaba-levels-in-a-mouse-model-of-alzheimer-s-disease
#18
Upasana Roy, Lara Stute, Corinna Höfling, Maike Hartlage-Rübsamen, Jörg Matysik, Steffen Roβner, A Alia
Age and sex are risk factors of Alzheimer's disease (AD). Among the neurotransmitter systems, gamma-aminobutyric acid (GABA) has been implicated in AD pathogenesis but the relevance of sex-specific GABAergic dysfunction during AD progression remains unknown. In the present study, we utilized state-of-the-art high-resolution magic angle spinning nuclear magnetic resonance to systematically monitor the brain region-, age-, and sex-specific modulation of GABA levels in wild-type and Tg2576 mice with amyloid pathology...
October 26, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/29153989/psen1-mutant-ipsc-derived-model-reveals-severe-astrocyte-pathology-in-alzheimer-s-disease
#19
Minna Oksanen, Andrew J Petersen, Nikolay Naumenko, Katja Puttonen, Šárka Lehtonen, Max Gubert Olivé, Anastasia Shakirzyanova, Stina Leskelä, Timo Sarajärvi, Matti Viitanen, Juha O Rinne, Mikko Hiltunen, Annakaisa Haapasalo, Rashid Giniatullin, Pasi Tavi, Su-Chun Zhang, Katja M Kanninen, Riikka H Hämäläinen, Jari Koistinaho
Alzheimer's disease (AD) is a common neurodegenerative disorder and the leading cause of cognitive impairment. Due to insufficient understanding of the disease mechanisms, there are no efficient therapies for AD. Most studies have focused on neuronal cells, but astrocytes have also been suggested to contribute to AD pathology. We describe here the generation of functional astrocytes from induced pluripotent stem cells (iPSCs) derived from AD patients with PSEN1 ΔE9 mutation, as well as healthy and gene-corrected isogenic controls...
November 12, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/29153610/tdp-43-proteolysis-is-associated-with-astrocyte-reactivity-after-traumatic-brain-injury-in-rodents
#20
Chih-Yuan Huang, Yi-Che Lee, Ping-Chia Li, Po-Chou Liliang, Kang Lu, Kuo-Wei Wang, Li-Ching Chang, Li-Yen Shiu, Ming-Feng Chen, Yuan-Ting Sun, Hao-Kuang Wang
The aggregation and deposition of transactivation response DNA-binding protein 43 (TDP-43) in neurons and astrocytes is characteristic in a number of neurodegenerative diseases including Alzheimer's disease, frontotemporal lobar degeneration, and amyotrophic lateral sclerosis. Nevertheless, the exact role of TDP-43 in astrocytes is unknown. Recently, TDP-43 was identified in neurons but not astrocytes after traumatic brain injury (TBI) in humans. In the present study, we evaluated TDP-43 expression and proteolysis in astrocytes in a rat model of TBI...
December 15, 2017: Journal of Neuroimmunology
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