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Da-Zhi Guo, Lin Xiao, Yi-Jun Liu, Chen Shen, Hui-Fang Lou, Yan Lv, Shu-Yi Pan
This study aimed to investigate the role of cathepsin D (CathD) in central nervous system (CNS) myelination and its possible mechanism. By using CathD knockout mice in conjunction with immunohistochemistry, immunocytochemistry and western blot assays, the myelination of the CNS and the development of oligodendrocyte lineage cells in vivo and in vitro were observed. Endocytosis assays, real-time-lapse experiments and total internal reflection fluorescence microscopy were used to demonstrate the location and movement of proteolipid protein in oligodendrocyte lineage cells...
March 16, 2018: Experimental & Molecular Medicine
Bahareh Nazari, Masoud Soleimani, Somayeh Ebrahimi Barough, Seyed Ehsan Enderami, Mansure Kazemi, Babak Negahdari, Esmaeil Sadroddiny, Jafar Ai
Oligodendrocytes play critical roles in the central nervous system (CNS) thorough producing myelin sheaths around axons. There are a variety of approaches to produce oligodendrocytes in vitro and in vivo which are a subject of interest in many studies. A new approach to induce this differentiation is using microRNA 219 (miR-219). However, this new approach suffers from a lack of studies regarding the effect of miR-219 on differentiating human induced pluripotent stem cells (hiPSCs) to oligodendrocytes. This study aimed to assess the impact of miR-219-overexpression on hiPSCs...
March 9, 2018: Journal of Chemical Neuroanatomy
Marie-Amélie Farreny, Eric Agius, Sophie Bel-Vialar, Nathalie Escalas, Nagham Khouri-Farah, Chadi Soukkarieh, Cathy Danesin, Fabienne Pituello, Philippe Cochard, Cathy Soula
BACKGROUND: Most oligodendrocytes of the spinal cord originate from ventral progenitor cells of the pMN domain, characterized by expression of the transcription factor Olig2. A minority of oligodendrocytes is also recognized to emerge from dorsal progenitors during fetal development. The prevailing view is that generation of ventral oligodendrocytes depends on Sonic hedgehog (Shh) while dorsal oligodendrocytes develop under the influence of Fibroblast Growth Factors (FGFs). RESULTS: Using the well-established model of the chicken embryo, we show that ventral spinal progenitor cells activate FGF signaling at the onset of oligodendrocyte precursor cell (OPC) generation...
March 8, 2018: Neural Development
Matthias Weider, Laura Julia Starost, Katharina Groll, Melanie Küspert, Elisabeth Sock, Miriam Wedel, Franziska Fröb, Christian Schmitt, Tina Baroti, Anna C Hartwig, Simone Hillgärtner, Sandra Piefke, Tanja Fadler, Marc Ehrlich, Corinna Ehlert, Martin Stehling, Stefanie Albrecht, Ammar Jabali, Hans R Schöler, Jürgen Winkler, Tanja Kuhlmann, Michael Wegner
Oligodendrocytes produce myelin for rapid transmission and saltatory conduction of action potentials in the vertebrate central nervous system. Activation of the myelination program requires several transcription factors including Sox10, Olig2, and Nkx2.2. Functional interactions among them are poorly understood and important components of the regulatory network are still unknown. Here, we identify Nfat proteins as Sox10 targets and regulators of oligodendroglial differentiation in rodents and humans. Overall levels and nuclear fraction increase during differentiation...
March 2, 2018: Nature Communications
Kouko Tatsumi, Ayami Isonishi, Miwako Yamasaki, Yoshie Kawabe, Shoko Morita-Takemura, Kazuki Nakahara, Yuki Terada, Takeaki Shinjo, Hiroaki Okuda, Tatsuhide Tanaka, Akio Wanaka
Astrocytes are the most abundant glia cell type in the central nervous system (CNS), and are known to constitute heterogeneous populations that differ in their morphology, gene expression and function. Although glial fibrillary acidic protein (GFAP) is the cardinal cytological marker of CNS astrocytes, GFAP-negative astrocytes can easily be found in the adult CNS. Astrocytes are also allocated to spatially distinct regional domains during development. This regional heterogeneity suggests that they help to coordinate post-natal neural circuit formation and thereby to regulate eventual neuronal activity...
2018: Frontiers in Neuroanatomy
Yuki Fujiwara, Wataru Miyazaki, Noriyuki Koibuchi, Takahiko Katoh
Environmental chemicals are known to disrupt the endocrine system in humans and to have adverse effects on several organs including the developing brain. Recent studies indicate that exposure to environmental chemicals during gestation can interfere with neuronal differentiation, subsequently affecting normal brain development in newborns. Xenoestrogen, bisphenol A (BPA), which is widely used in plastic products, is one such chemical. Adverse effects of exposure to BPA during pre- and postnatal periods include the disruption of brain function...
2018: Frontiers in Endocrinology
Aditi Falnikar, Jarred Stratton, Ruihe Lin, Carrie E Andrews, Ashley Tyburski, Victoria A Trovillion, Chelsea Gottschalk, Biswarup Ghosh, Lorraine Iacovitti, Melanie B Elliott, Angelo C Lepore
Populations of neural stem cells (NSCs) reside in a number of defined niches in the adult CNS where they continually give rise to mature cell types throughout life, including newly-born neurons. In addition to prototypical niches of the subventricular zone and subgranular zone of the hippocampal dentate gyrus, novel stem cell niches that are also neurogenic have recently been identified in multiple midline structures, including circumventricular organs (CVOs) of the brain. These resident NSCs may have the potential for reparative processes in pathologies such as traumatic spinal cord injury (SCI) and traumatic brain injury (TBI)...
February 22, 2018: Journal of Neurotrauma
Mayu Nishimuta, Kenta Masui, Tomoko Yamamoto, Yuichi Ikarashi, Katsutoshi Tokushige, Etsuko Hashimoto, Yoji Nagashima, Noriyuki Shibata
We present a case of hepatolenticular degeneration, so-called Wilson's disease (WD), in a 31-year-old Japanese man with broader deposition of copper in the liver, kidney and brain. The liver showed severe cirrhotic changes with macronodular pseudolobule formation, but there was little difference in immunohistochemical expression patterns of the copper transporter ATP7B between the control and present case. In the brain, there were both WD-related lesions such as the scattering of Opalski cells and changes caused by hepatic encephalopathy including the appearance of Alzheimer type II glia...
February 21, 2018: Neuropathology: Official Journal of the Japanese Society of Neuropathology
Jiri Ruzicka, Lucia Machova Urdzikova, Barbora Svobodova, Anubhav G Amin, Kristyna Karova, Jana Dubisova, Kristyna Zaviskova, Sarka Kubinova, Meic Schmidt, Meena Jhanwar-Uniyal, Pavla Jendelova
Systematic inflammatory response after spinal cord injury (SCI) is one of the factors leading to lesion development and a profound degree of functional loss. Anti-inflammatory compounds, such as curcumin and epigallocatechin gallate (EGCG) are known for their neuroprotective effects. In this study, we investigated the effect of combined therapy of curcumin and EGCG in a rat model of acute SCI induced by balloon compression. Immediately after SCI, rats received curcumin, EGCG, curcumin + EGCG or saline [daily intraperitoneal doses (curcumin, 6 mg/kg; EGCG 17 mg/kg)] and weekly intramuscular doses (curcumin, 60 mg/kg; EGCG 17 mg/kg)] for 28 days...
January 2018: Neural Regeneration Research
Jin Kim, Hanseul Oh, Bokyeong Ryu, Ukjin Kim, Ji Min Lee, Cho-Rok Jung, C-Yoon Kim, Jae-Hak Park
Triclosan (TCS) is an organic compound with a wide range of antibiotic activity and has been widely used in items ranging from hygiene products to cosmetics; however, recent studies suggest that it has several adverse effects. In particular, TCS can be passed to both fetus and infants, and while some evidence suggests in vitro neurotoxicity, there are currently few studies concerning the mechanisms of TCS-induced developmental neurotoxicity. Therefore, this study aimed to clarify the effect of TCS on neural development using zebrafish models, by analyzing the morphological changes, the alterations observed in fluorescence using HuC-GFP and Olig2-dsRED transgenic zebrafish models, and neurodevelopmental gene expression...
February 2, 2018: Environmental Pollution
Maria C Estevez-Silva, Akshitha Sreeram, Stephanie Cuskey, Nikolai Fedorchak, Nisha Iyer, Randolph S Ashton
BACKGROUND: Transplantation of human pluripotent stem cell (hPSC)-derived neurons into chick embryos is an established preliminary assay to evaluate engraftment potential. Yet, with recent advances in deriving diverse human neuronal subtypes, optimizing and standardizing such transplantation methodology for specific subtypes at their correlated anatomical sites is still required. NEW METHOD: We determined the optimal stage of hPSC-derived motor neuron (hMN) differentiation for ex ovo transplantation, and developed a single injection protocol that implants hMNs throughout the spinal cord enabling broad regional engraftment possibilities...
February 3, 2018: Journal of Neuroscience Methods
Fan Yang, Xiao Feng, Arndt Rolfs, Jiankai Luo
Niemann-Pick Type C (NPC) disease is a rare neurovisceral disorder caused by mutations of either NPC1 or NPC2 gene and characterized by defective intracellular transport of cholesterol and glycosphingolipids, leading to neuron loss and myelin aberration in the central nervous system. In this study, by comparing protein expression in the cortical white matter tracts from mice at different postnatal days, we identified that in the NPC1 mutant (NPC1-/-) mice, the onset of myelination is delayed and the amount of the major myelin protein MBP and PLP, and oligodendrocyte regulatory factor Olig1 and Olig2, but not NG2 and Sox10, decreased significantly, suggesting a disruption of oligodendrocyte differentiation...
March 15, 2018: Journal of the Neurological Sciences
Lauren M Watson, Maggie M K Wong, Jane Vowles, Sally A Cowley, Esther B E Becker
The establishment of a reliable model for the study of Purkinje cells in vitro is of particular importance, given their central role in cerebellar function and pathology. Recent advances in induced pluripotent stem cell (iPSC) technology offer the opportunity to generate multiple neuronal subtypes for study in vitro. However, to date, only a handful of studies have generated Purkinje cells from human pluripotent stem cells, with most of these protocols proving challenging to reproduce. Here, we describe a simplified method for the reproducible generation of Purkinje cells from human iPSCs...
February 3, 2018: Cerebellum
Andreas Sagner, Zachary B Gaber, Julien Delile, Jennifer H Kong, David L Rousso, Caroline A Pearson, Steven E Weicksel, Manuela Melchionda, S Neda Mousavy Gharavy, James Briscoe, Bennett G Novitch
During tissue development, multipotent progenitors differentiate into specific cell types in characteristic spatial and temporal patterns. We addressed the mechanism linking progenitor identity and differentiation rate in the neural tube, where motor neuron (MN) progenitors differentiate more rapidly than other progenitors. Using single cell transcriptomics, we defined the transcriptional changes associated with the transition of neural progenitors into MNs. Reconstruction of gene expression dynamics from these data indicate a pivotal role for the MN determinant Olig2 just prior to MN differentiation...
February 2018: PLoS Biology
Hao Zuo, William M Wood, Amin Sherafat, Robert A Hill, Q Richard Lu, Akiko Nishiyama
NG2 cells are a resident glial progenitor cell population that is uniformly distributed throughout the developing and mature mammalian central nervous system (CNS). Those in the postnatal CNS generate exclusively myelinating and non-myelinating oligodendrocytes and are hence equated with oligodendrocyte precursor cells (OPCs). Prenatally, NG2 cells in the ventral gray matter of the forebrain generate protoplasmic astrocytes as well as oligodendrocytes. The fate conversion from NG2 cells into protoplasmic astrocytes is dependent on downregulation of the key oligodendrocyte transcription factor Olig2...
January 30, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Takahiro Seyama, Yoshimasa Kamei, Takayuki Iriyama, Shinya Imada, Mari Ichinose, Masatake Toshimitsu, Tomoyuki Fujii, Hiroaki Asou
AIM: Antenatal maternal administration of magnesium sulfate (MgSO4 ) reduces cerebral palsy in preterm infants. However, it remains controversial as to whether it also reduces occurrence of white matter damage, or periventricular leukomalacia. We assessed the effect of MgSO4 against white matter damage induced by hypoxic-ischemic insult using a neonatal rat model and culture of premyelinating oligodendrocytes (pre-OL). METHODS: Rat pups at postnatal day (P) 6 were administered either MgSO4 or vehicle intraperitoneally before hypoxic-ischemic insult (unilateral ligation of the carotid artery followed by 6% oxygen for 1 h)...
January 23, 2018: Journal of Obstetrics and Gynaecology Research
Arvind Palanisamy, Ramaswamy Kannappan, Zhiqiang Xu, Audrey Martino, Matthew B Friese, Justin D Boyd, Gregory Crosby, Deborah J Culley
Synthetic oxytocin (sOT) is widely used during labor, yet little is known about its effects on fetal brain development despite evidence that it reaches the fetal circulation. Here, we tested the hypothesis that sOT would affect early neurodevelopment by investigating its effects on neural progenitor cells (NPC) from embryonic day 14 rat pups. NPCs expressed the oxytocin receptor (OXTR), which was downregulated by 45% upon prolonged treatment with sOT. Next, we examined the effects of sOT on NPC death, apoptosis, proliferation, and differentiation using antibodies to NeuN (neurons), Olig2 (oligodendrocytes), and GFAP (astrocytes)...
2018: PloS One
Shahnaz Razavi, Nazem Ghasemi, Mohammad Mardani, Hossein Salehi
OBJECTIVES: The presence of neurotrophic factors is critical for regeneration of neural lesions. Here, we transplanted combination of neurotrophic factor secreting cells (NTF-SCs) and human adipose derived stem cells (hADSCs) into a lysolecithin model of multiple sclerosis (MS) and determined the myelinization efficiency of these cells. MATERIALS AND METHODS: In this experimental study, 50 adult rats were randomly divided into five groups: control, lysolecithin, vehicle, hADSCs transplantation and NTF-SCs/ hADSCs co-transplantation group...
April 2018: Cell Journal
Mubeena Pm Mariyath, Mehdi Hayat Shahi, Shirin Farheen, Mohd Tayyab, Nabeela Khanam, Asif Ali
BACKGROUND: Complex central nervous system (CNS) is made of neuronal cells and glial cells. Cells of central nervous system are able to regenerate after injury and during repairing. Sonic hedgehog pathway initiated by Shh-N a glycoprotein plays vital role in CNS patterning growth, development and now tumorigenesis. Nkx2.2 homeodomain transcription factor is an effecter molecule, which is positively regulated by Shh during normal growth. Nkx2.2 is essential for V3 domain specification during neural tube patterning at embryonic stage...
January 1, 2018: Current Cancer Drug Targets
Qiang Lyu, Zi-Bin Zhang, Song-Jun Fu, Liu-Lin Xiong, Jing Liu, Ting-Hua Wang
Traumatic brain injury (TBI) may cause neurological damage, but an effective therapy and the associated mechanisms of action have not yet been elucidated. A TBI model was established using the modified Feeney method. A2B5+ cells, an oligodendroglial progenitor, were acquired from induced pluripotent stem cells (iPSCs) by mouse embryonic fibroblasts and were transplanted into the injured site. The neurological severity score (NSS) was recorded on 3 d, 7 d, 11 d, 15 d, and 19 d. Seven days after transplantation, oligodendrocytes 2 (Olig2) and myelin basic protein (MBP) were detected by immunohistochemistry (IHC) and Western blot (WB), and long noncoding RNAs (lncRNAs) and messenger RNAs (mRNAs) were screened by microarray technology...
October 2017: Cell Transplantation
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