TOP ＞ シンポジウム

シンポジウム The ins and outs of neuro-vascular interactions 1S4-1 Interaction between glia and blood vessels during cortical development Tabata Hidenori1，Sasaki Megumi2，Inaguma Yutaka1，Ito Hidenori1，Takebayashi Hirohide3，Ema Masatsugu4，Ikenaka Kazuhiro5，Nagata Koh-ichi1，Nakajima Kazunori2 1Dept of Mol Neurobiol, Inst for Dev Res, Aichi Human Service Cent，2Dept Anat, Keio Univ Sch of Med，3Div of Neurobiol ＆ Anat, Grad Sch of Med ＆ Den Sci, Niigata Univ，4Dept Stem Cells ＆ Human Disease Models, Res Cent for Animal Life Sci, Shiga Univ of Med Sci，5Div of Neurobiol ＆ Bioinformatics During cerebral cortical development, neurons and glia are produced directly or indirectly from neural stem cells in the ventricular zone and migrate to their final destinations. Although the behaviors of migrating neurons are well described, those of glial progenitors are not largely uncovered. The most accepted model of the migration of glial progenitor is the translocation of radial glia, but this model does not explain the even distribution of astrocytes throughout the all layers of cortical gray matter. During our observations of the cells migrating from the ventricular zone, we have noticed that some cells moved in a very unique manner that had not been previously described：these cells moved very rapidly and almost randomly within both the intermediate zone and the cortical plate and frequently underwent cell division. We named this migration erratic migration. The lineage analyses of them both in vitro and in vivo revealed that they were astrocyte progenitors destined for cortical gray matter. These cells frequently migrate along blood vessels and spread widely throughout the cortical plate. 1S4-2 Macrophage-independent programmed regression of fetal ocular vasculature triggered by neurons Kubota Yoshiaki Department of Vacular Biology, School of Medicine, Keio University Vascular development involves not only vascular growth but also regression of transient or unnecessary vasculature such as ductus arteriosus and umbilical arteries. Hyaloid vasculature is the temporary circulatory system in fetal eyes, which normally degenerates soon after birth. Failure to regress these vessels leads to an ocular pathology called the persistent hyperplastic primary vitreous, which causes severe intraocular hemorrhage and impairs visual function. This programmed regression of hyaloid vessels is generally thought to be triggered by ocular macrophages inducing endothelial cell death. Here, we found a novel switch of this regression controlled by neurons independently of macrophages. Striking upregulation of VEGFR2 occurs in retinal neurons just after birth via activation of the Distal-Multipotent-Mesodermal-Enhancer（DMME）, known as a hemangioblast-specific enhancer of VEGFR2. Lack of neuronal VEGFR2 interrupts this program resulting in massive hyaloid vessels that persist even during late postnatal days. This abnormality is caused by excessive VEGF proteins in the vitreous cavity due to the impairment in neuronal endocytosis of VEGF, recently described to account for neuronal avascularity in neonatal retinas. Taken together our data indicate neurons trigger transition from the fetal to the postnatal circulatory systems in retina independently of macrophages. 1S4-3 Role of blood vessels in neuronal regeneration Sawamoto Kazunobu Dept. of Dev. ＆ Regen. Biol., Nagoya City Univ. Neuronal migration is an important process in brain development and homeostasis. It occurs in the adult brain, following adult neurogenesis, not only in the embryonic brain. In fact, throughout life, numerous new neurons generated by stem cells in the adult ventricular-subventricular zone（V-SVZ）take the long journey to the olfactory bulb（OB）through the rostral migratory stream（RMS）. The neural stem cells in the adult V-SVZ also have the capacity to partially regenerate new neurons after various insults. After ischemic injury in rodents, the V-SVZ-derived new neurons migrate from the V-SVZ towards the injured site along blood vessels. In this talk, I will present recent studies on the molecular mechanisms of the blood vessel-guided neuronal migration. Our in vivo and in vitro data suggest that cell-to-cell interactions mediated by the laminin-integrin signaling is important for the efficient chain migration of new neurons along the blood vessel scaffold. Transplantation of laminin-rich porous sponge promoted the migration of new neurons towards the injured cortex, suggesting that artificial blood vessel-like scaffold may enhance regenerative property of endogenous new neurons in the brain. 1S4-4 Control of oligodendrocyte precursor cell survival and proliferation by vascular endothelial cells Ishizaki Yasuki Mol. Cell. Neurobiol., Gunma Univ. Grad. Sch. Med We showed previously that transplantation of brain microvascular endothelial cells（MVECs）greatly stimulated remyelination in the white matter lesion induced by endothelin-1（ET-1）injection and improved the behavioral outcome（Puentes et al., 2012）. In this study, we examined the effects of MVECs on the behavior of oligodendrocyte precursor cells（OPCs）in vivo and in vitro. MVECs prepared from rat cerebral cortices were transplanted into ET-1-induced demyelinating lesion in the internal capsule（IC）of rat brains. Cell density, apoptotic death, and proliferative state of OPCs in and around the ET-1-induced lesions in IC of MVEC-transplanted animals were examined. The effects of exosomes prepared from MVEC cultures on survival and proliferation of OPCs isolated from cerebra of young rats were also examined. MVECs promoted survival of OPCs both in vivo and in vitro and stimulated their proliferation in vitro. Elucidation of the molecular mechanisms by which MVECs control survival and proliferation of OPCs may lead to the establishment of a therapeutic strategy against demyelinating diseases. 1S4-5 Vascular and neurogenic rejuvenation of the aging mouse brain by youngsystemic factors Buchanan Sean M.，Katsimpardi Lida，Rubin Lee L. The Department of Stem Cell and Regenerative Biology, Harvard University Recent work from our lab and others has come to the surprisingconclusion that some aspects of aging are reversible and are under thecontrol of circulating factors. Parabiotic coupling of young and oldmice has demonstrated that systemic factors present in young blood canpromote improvements in the aged nervous system including enhancedvasculature and blood flow in the CNS, augmented neurogenesis in theadult brain, and increased performance in behavioral tests. Inparticular, we find that systemic administration of growthdifferentiation factor 11（GDF11）, a TGFβ family member that decreaseswith aging, can recapitulate some of the beneficial aspects of youngblood. Additionally, we find that GDF11 and its receptors areexpressed within the central nervous system, and that neurons and gliarespond to direct stimulation with the ligand. These findings haveimportant clinical implications and may form the basis for novelavenues of treating age related neurological decline.