論文 - 岡野　栄之

MicroRNAs in neural stem cells and neurogenesis

岡野 栄之

FRONTIERS IN NEUROSCIENCE 6   S347 - S348 2012年

研究論文（学術雑誌）,  ISSN  1662-453X

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NOTCH SIGNALING AND THE DEVELOPING INNER EAR

岡野 栄之

NOTCH SIGNALING IN EMBRYOLOGY AND CANCER 727   161 - 173 2012年

研究論文（学術雑誌）,  ISSN  0065-2598

Usefulness of human disease-specific iPS cells research for understanding of age-related higher brain dysfunction

岡野 栄之

JOURNAL OF PHARMACOLOGICAL SCIENCES 118   124P - 124P 2012年

研究論文（学術雑誌）,  ISSN  1347-8613

Nestin Protein Is Phosphorylated in Adult Neural Stem/Progenitor Cells and Not Endothelial Progenitor Cells

岡野 栄之

STEM CELLS INTERNATIONAL    1410 - 1422 2012年

研究論文（学術雑誌）,  ISSN  1687-966X

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Renin-angiotensin system hyperactivation can induce inflammation and retinal neural dysfunction

Kurihara Toshihide, Ozawa Yoko, Ishida Susumu, Okano Hideyuki, Tsubota Kazuo

International Journal of Inflammation 2012 2012年

ISSN  2090-8040

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<p>The renin-angiotensin system (RAS) is a hormone system that has been classically known as a blood pressure regulator but is becoming well recognized as a proinflammatory mediator. In many diverse tissues, RAS pathway elements are also produced intrinsically, making it possible for tissues to respond more dynamically to systemic or local cues. While RAS is important for controlling normal inflammatory responses, hyperactivation of the pathway can cause neural dysfunction by inducing accelerated degradation of some neuronal proteins such as synaptophysin and by activating pathological glial responses. Chronic inflammation and oxidative stress are risk factors for high incidence vision-threatening diseases such as diabetic retinopathy (DR), age-related macular degeneration (AMD), and glaucoma. In fact, increasing evidence suggests that RAS inhibition may actually prevent progression of various ocular diseases including uveitis, DR, AMD, and glaucoma. Therefore, RAS inhibition may be a promising therapeutic approach to fine-tune inflammatory responses and to prevent or treat certain ocular and neurodegenerative diseases. © 2012 Toshihide Kurihara et al.</p>

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Derivation of induced pluripotent stem cells by retroviral gene transduction in mammalian species

Imamura Masanori, Okuno Hironobu, Tomioka Ikuo, Kawamura Yoshimi, Lin Zachary Yu Ching, Nakajima Ryusuke, Akamatsu Wado, Okano Hirotaka James, Matsuzaki Yumi, Sasaki Erika, Okano Hideyuki

  21 - 48 2012年

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<p>Pluripotent stem cells can provide us with an enormous cell source for in vitro model systems for development. In 2006, new methodology was designed to generate pluripotent stem cells directly from somatic cells, and these cells were named induced pluripotent stem cells (iPSCs). This method consists of technically simple procedures: donor cell preparation, gene transduction, and isolation of embryonic stem cell-like colonies. The iPSC technology enables cell biologists not only to obtain pluripotent stem cells easily but also to study the reprogramming events themselves. Here, we describe the protocols to generate iPSCs from somatic origins by using conventional viral vectors. Specifically, we state the usage of three mammalian species: mouse, common marmoset, and human. As mouse iPSC donors, fibroblasts are easily prepared, while mesenchymal stem cells are expected to give rise to highly reprogrammed iPSCs efficiently. Common marmoset (Callithrix jacchus), a nonhuman primate, represents an alternative model to the usual laboratory animals. Finally, patient-specific human iPSCs give us an opportunity to examine the pathology and mechanisms of dysregulated genomic imprinting. The iPSC technology will serve as a valuable method for studying genomic imprinting, and conversely, the insights from these studies will offer valuable criteria to assess the potential of iPSCs. © 2012 Springer Science+Business Media, LLC.</p>

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Notch signaling and the developing inner ear

Murata Junko, Ikeda Katsuhisa, Okano Hideyuki

  161 - 173 2012年

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<p>Sensory hair cells (HCs) and their associated nonsensory supporting cells (SCs) exhibit a typical mosaic pattern in each of the sensory patches in the inner ear. Notch signaling has been considered to conduct the formation of this mosaic pattern through one of its famous functions, known as 'lateral inhibition'. The two Notch ligands Delta-like1 and Jagged2 are believed to act synergistically at the stage of cell diversification in mammals. In addition, many current studies suggest that Notch signaling has another inductive, but not inhibiting, role in the determination of the prosensory region, which precedes the cell diversification of HCs and SCs and Jagged1 is thought to be an essential ligand in this process. Earlier in ear development, the first cell fate determination begins with the delamination of the neuroblasts from the otic epithelium. The delaminated neuroblasts migrate and coalesce to form cochleovestibular ganglion. Notch signaling pathway is thought to function during the delamination through its lateral inhibitory mechanism. Recently, many experiments examining Notch-related gene expression patterns and direct functional analyses of genes have revealed multiple important functions of Notch in inner ear development. Here, we survey a series of studies and discuss the issues that remain to be elucidated in the future. © 2012 Landes Bioscience and Springer Science+Business Media.</p>

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Regeneration of the damaged CNS using human iPSCs-derived neural progenitor cells

Okano Hideyuki

Clinical Neurology 52 （ 11 ） 1147 2012年

ISSN  0009-918X

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Modeling familial alzheimer's disease with induced pluripotent stem cells

Yagi Takuya, Ito Daisuke, Okada Yohei, Akamatsu Wado, Nihei Yoshihiro, Okano Hideyuki, Suzuki Norihiro

Clinical Neurology 52 （ 11 ） 1134 - 1136 2012年

ISSN  0009-918X

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<p>Alzheimer's disease (AD) is the most common form of age-related dementia, characterized by progressive memory loss and cognitive disturbance. According to the amyloid cascade hypothesis, a prevailing theory of AD pathology, accumulation of toxic Aβ42, in the brain is the initiator of AD pathogenesis, subsequently leading to the formation of neurofibrillary tangles, and consequently neuronal loss. Mutations of presenilin 1 (PS1) and presenilin 2(PS2), which are catalytic components of γ-secretase, are causative factors for autosomal dominant early-onset familial AD (FAD). Induced pluripotent stem cell (iPSC) technology provides a new method for elucidating the molecular basis of human diseases, including neurodegenerative diseases. Here we generate iPSCs from fibroblasts of FAD patients with mutations in PS1 (A246E) and PS2 (N141I), and characterize the differentiation of these cells into neurons. We find that FAD-iPSC-derived differentiated neurons have increased toxic Aβ42 secretion, recapitulating the molecular pathogenesis of mutant presenilins. Furthermore, secretion of Aβ42 from these neurons sharply responds to γ secretase inhibitors and modulators, indicating the potential for identification and validation of candidate drugs. Our findings demonstrate that the FAD-iPSC-derived neuron is a valid model of AD and provides an innovative strategy for the study of late-onset neurodegenerative diseases.</p>

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Investigation of pathophysiology of Parkinson's disease using iPS cells technology

Okano Hideyuki

Clinical Neurology 52 （ 11 ） 899 2012年

ISSN  0009-918X

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Cisterna-specific localization of glycosylation-related proteins to the Golgi apparatus

Yamamoto-Hino Miki, Abe Masato, Shibano Takako, Setoguchi Yuka, Awano Wakae, Ueda Ryu, Okano Hideyuki, Goto Satoshi

Cell Structure and Function 37 （ 1 ） 55 - 63 2012年

ISSN  0386-7196

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<p>The Golgi apparatus is an intracellular organelle playing central roles in post-translational modification and in the secretion of membrane and secretory proteins. These proteins are synthesized in the endoplasmic reticulum (ER) and transported to the cis-, medial- and trans-cisternae of the Golgi. While trafficking through the Golgi, proteins are sequentially modified with glycan moieties by different glycosyltransferases. Therefore, it is important to analyze the glycosylation function of the Golgi at the level of cisternae. Markers widely used for cis-, medial- and trans-cisternae/trans Golgi network (TGN) in Drosophila are GM130, 120 kDa and Syntaxin16 (Syx16); however the anti-120 kDa antibody is no longer available. In the present study, Drosophila Golgi complex-localized glycoprotein-1 (dGLG1) was identified as an antigen recognized by the anti-120 kDa antibody. A monoclonal anti-dGLG1 antibody suitable for immunohistochemistry was raised in rat. Using these markers, the localization of glycosyltransferases and nucleotide-sugar transporters (NSTs) was studied at the cisternal level. Results showed that glycosyltransferases and NSTs involved in the same sugar modification are localized to the same cisternae. Furthermore, valuable functional information was obtained on the localization of novel NSTs with as yet incompletely characterized biochemical properties, © 2012 by Japan Society for Cell Biology.</p>

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Novel Method for Analyzing Locomotor Ability after Spinal Cord Injury in Rats: Technical Note

岡野 栄之

NEUROLOGIA MEDICO-CHIRURGICA 53 （ 12 ） 907 - 913 2013年12月

研究論文（学術雑誌）,  ISSN  0470-8105

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Olfactory cells via nasal biopsy reflect the developing brain in gene expression profiles: Utility and limitation of the surrogate tissues in research for brain disorders

岡野 栄之

NEUROSCIENCE RESEARCH 77 （ 4 ） 247 - 250 2013年12月

研究論文（学術雑誌）,  ISSN  0168-0102

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Multidimensional MRI-CT atlas of the naked mole-rat brain (Heterocephalus glaber)

岡野 栄之

FRONTIERS IN NEUROANATOMY 7   2462 - 2469 2013年12月

研究論文（学術雑誌）,  ISSN  1662-5129

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In vivo tracing of neural tracts in tiptoe-walking yoshimura mice by diffusion tensor tractography

Takano Morito, Komaki Yuji, Hikishima Keigo, Konomi Tsunehiko, Fujiyoshi Kanehiro, Tsuji Osahiko, Okano Hideyuki, Toyama Yoshiaki, Nakamura Masaya

  107 - 117 2013年11月

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<p>In ossification of the posterior longitudinal ligaments (OPLL), axonal disruption results in motor and sensory function impairment. Twy (tiptoe-walking Yoshimura) mice develop spontaneous calcification in the cervical ligaments, thereby causing chronic compression of the spinal cords. To determine whether in vivo diffusion tensor tractography (DTT) can evaluate the axonal disruption of the chronic compressive spinal cords in twy mice, 6-, 15-, and 20-week-old twy mice were chronologically subjected to DTT. MRI was performed using a 7.0-Tesla magnet with a surface coil (CryoProbe). Diffusion tensor images were analyzed using TrackVis (Massachusetts General Hospital, MA, USA). We succeeded in depicting in vivo high-resolution DTT of the twy mice. The progress of the ligamentous calcification was observed at C2-3 level in each twy mouse, and the number of RT-97 or SMI31 positive fibers was decreased depending on the severity of the compression of the spinal cord. Quantitative analysis of sequential DTT enabled to detect subtle damage of the compressed spinal cord prior to the deterioration of neurological function in twy mice. Thus, in a clinical setting, DTT could be a new effective imaging modality in patients with cervical OPLL.</p>

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Regenerative medicine for spinal cord injury utilizing iPS cells

Tsuji Osahiko, Nori Satoshi, Kobayashi Yoshiomi, Fujiyoshi Kanehiro, Okano Hideyuki, Toyama Yoshiaki, Nakamura Masaya

  229 - 245 2013年11月

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<p>Reports of functional recovery from spinal cord injury (SCI) after the transplantation of rat-fetus-derived neural stem/precursor cells (NS/PCs) and murine embryonic stem cells (ES cells) have raised great expectations for the successful clinical trial of stem cell transplantation therapy. However, the ethical issues concerning about destroying human embryos or fertilized oocytes to obtain such stem cells have been a major impediment to developing clinically useful stem cell sources and to use them in clinical applications. Recently, induced pluripotent stem cells (iPS cells), which can serve as a source of autologous cell transplantation, have been attracting a lot of attention as a clinically practical alternative to stem cells obtained directly from tissues. In this chapter, we outline the neural induction of murine and human iPS cells, their therapeutic efficacy in mouse and primate SCI models, and their safety in vivo.</p>

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Recombinant human hepatocyte growth factor promotes functional recovery after spinal cord injury

Kitamura Kazuya, Iwanami Akio, Fujiyoshi Kanehiro, Yamane Jun Ichi, Hikishima Keigo, Funakoshi Hiroshi, Nakamura Toshikazu, Aoki Masashi, Toyama Yoshiaki, Okano Hideyuki, Nakamura Masaya

  147 - 167 2013年11月

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<p>Hepatocyte growth factor (HGF), which is a potent mitogen for mature hepatocytes and a mediator of the inflammatory responses to tissue injury, was recently highlighted as a potent neurotrophic factor in the central nervous system. We revealed that introducing exogenous HGF into the injured rat spinal cord using a herpes simplex virus-1 vector significantly reduces the area of damaged tissue and promotes functional recovery. However, this rat study did not examine the therapeutic effects of administering HGF after injury, which is the most critical issue for clinical application. To translate this strategy to human treatment, we induced a contusive cervical SCI in the common marmoset, a primate, and then administered recombinant human HGF (rhHGF) intrathecally. Motor function was assessed using an original open-field scoring system focusing on manual function, including reach-and-grasp performance and hand placement in walking. The intrathecal rhHGF preserved the corticospinal fibers and myelinated areas, thereby promoting functional recovery. This study demonstrates the therapeutic effects, safety, and clinical efficacy of intrathecal rhHGF treatment for SCI in adult nonhuman primates and the possibility that this novel therapy may be suitable for clinical application.</p>

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Assessment of injured spinal cord using diffusion tensor tractography

Fujiyoshi Kanehiro, Konomi Tsunehiko, Tsuji Osahiko, Yamada Masayuki, Hikishima Keigo, Momoshima Suketaka, Okano Hideyuki, Toyama Yoshiaki, Nakamura Masaya

  345 - 365 2013年11月

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<p>In spinal cord injury (SCI), the evaluation of axonal fibers is important to assess the severity of injury and efficacy of any treatment protocol, but conventional methods such as tracer injection in the brain parenchyma are highly invasive and require histological evaluation, precluding clinical applications. Magnetic resonance imaging (MRI) is essential for predicting prognosis and planning treatment of patients with SCI noninvasively. However, the information provided by conventional T1- and T2-weighted MRI of the spinal cord is essentially limited to the differentiation of the white matter from the gray matter. By contrast, diffusion-weighted magnetic resonance imaging (DWI) provides much information about biological structures. In particular, diffusion tensor imaging (DTI) and diffusion tensor tractography (DTT) are powerful tools for evaluating white matter fibers in the central nervous system. We previously established a reproducible SCI model in adult common marmosets and demonstrated that DTT could be used to trace the neural tracts in the intact and injured spinal cord of these animals in vivo. Recently, many reports using DTT to analyze the spinal cord area have been published. Based on the findings from our experimental studies, we are now routinely performing DTT of the human spinal cord clinically. In this chapter, we outline the basic principles of DTT and describe the characteristics, limitations, and clinical application of DTT in the spinal cord.</p>

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Chondroitin sulphate N-acetylgalactosaminyl-transferase-1 inhibits recovery from neural injury

岡野 栄之

NATURE COMMUNICATIONS 4   106 - 114 2013年11月

研究論文（学術雑誌）,  ISSN  2041-1723

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A homozygous nonsense mutation in the gene for Tmem79, a component for the lamellar granule secretory system, produces spontaneous eczema in an experimental model of atopic dermatitis

岡野 栄之

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY 132 （ 5 ） 1111 - + 2013年11月

研究論文（学術雑誌）,  ISSN  0091-6749

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