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Symposium 29 Vascular-signpost in the nervous system guides its development and disease -from basic science to applied science シンポジウム29 アジア太平洋神経化学会（APSN）／日本神経化学会 ジョイントシンポジウム SY29-1 Cross-talk between nervous and vascular systems is essential for neocortical development 神経系と血管系の相互作用は、大脳皮質の発生に必要不可欠である Mizutani Ken-Ichi（水谷 健一） Kobe Gakuin University To facilitate efficient oxygen and nutrient delivery, blood vessels in the brain form three-dimensional patterns. However, little is known about how blood vessels develop stereographically in the neocortex and how they control the expansion and differentiation of neural progenitors during neocortical development. To observe the three-dimensional patterns of growing blood vessels during neocortical development better, we examined systematically Flt1-tandem dsRed BAC transgenic mice that expressed a fluorescent marker exclusively in vascular endothelial cells. We show that highly vascularized and avascular regions are strictly controlled in a spatially and temporally restricted manner and are associated with distinct cell populations. Therefore, not all blood vessels are associated equally with neural progenitors. Furthermore, a disruption of normal vascular patterning can induce abnormalities in neural development, whereas the impaired features of neural progenitors influenced angiogenesis patterning. These results indicate that the cross-talk between the nervous and vascular systems is essential for neocortex assembly. SY29-2 Neurovascular interaction is required for central nervous system regeneration 脳神経回路の修復を制御するメカニズム Muramatsu Rieko（村松 里衣子） Department. of Molecular Pharmacology, National Institute of Neuroscience, NCNP Demyelination in the central nervous system (CNS) leads to severe neurological deficits that can be partially reversed by spontaneous remyelination. Because the CNS is isolated from the peripheral milieu by the blood-brain barrier, remyelination is thought to be controlled by the CNS microenvironment. However, in this work we found that factors derived from peripheral tissue leak into the CNS after injury and promote remyelination in a murine model of toxin-induced demyelination. Mechanistically, leakage of circulating fibroblast growth factor 21 (FGF21), which is predominantly expressed by the pancreas, drives proliferation of oligodendrocyte precursor cells (OPCs) through interactions with β-klotho, an essential coreceptor of FGF21. We further confirmed that human OPCs expressed β-klotho and proliferated in response to FGF21 in vitro. Vascular barrier disruption is a common feature of many CNS disorders; thus, our findings reveal a potentially important role for the peripheral milieu in promoting CNS regeneration. SY29-3 Biomaterial engineering for angiogenesis after ischemic stroke 虚血性脳卒中の血管新生を促進させる生体材料工学的アプローチ Ajioka Itsuki（味岡 逸樹） Center for Brain Integration Research (CBIR), Tokyo Medical and Dental University (TMDU) Ischemic brain stroke is caused by blood flow interruption, leading to focal ischemia, neuron death, and motor, sensory and/or cognitive dysfunctions. Since stroke mortality has been declining, public concern has focused on the quality of life (QOL) for stoke patients. Although our brain is thought not to regenerate after injury, recent studies shed light on bringing out regeneration potential by biological and biomaterial-engineering approaches. Angiogenesis, neovascularization from existing blood vessel, is essential for tissue growth and repair. Newly generated blood vessel carry oxygen and nutrients for cell survival and growth. Vascular endothelial growth factor (VEGF) is a critical growth factor for angiogenesis. VEGF is a secreted protein and binds to its receptors on endothelial cells. VEGF promotes the proliferation, the survival, and the migration of endothelial cells and the gene expression of extracellular matrix (ECM) degradation enzyme. All of these VEGF functions play a key role during angiogenesis. Since brain stroke is caused by blood flow interruption, pro-angiogenic therapy is promising for preventing excess neuron death and improving functional recovery. Indeed, VEGF injection after stroke enhances angiogenesis, neuroprotection, and neurological recovery. However, VEGF needs to be delivered by cost-ineffective continuous infusion for angiogenic activity in ischemic brain. We previously developed porous sponge biomaterials generated from basement membrane (BM) matrix for the 3-dimentional culture of neurons and for the migration scaffolds of neuroblasts in injured cerebral cortex. In this presentation, I report and discuss the oriented immobilization of VEGF on LN-sponge via affinity interaction to develop angiogenic biomaterials. SY29-4 Hydrogel-based tissue engineering toolkits for 3D imaging and regenerative medicine Sun Woong Department of Anatomy and BK 21 Plus Program, Korea University College of Medicine, Korea Exploration of the 3D structures of intact organs at the cellular level is important for the understanding of the biological system. Advances in tissue clearing techniques allow the visualization of cellular structures inside the unsectioned whole organs. We have recently established the rapid and highly reproducible ACT-PRESTO (active clarity technique-pressure related efficient and stable transfer of macromolecules into organs) method that clears tissues or the whole body very quickly, while preserving tissue architecture and protein or mRNA signals within. Furthermore, we optimized ACT protocol for better visualization of vasculature by selective capture of extracellular matrix proteins with infused hydrogel, which we named CASPER. Because CASPSERized tissues maintain structural complexity and biological functions such as promoting angiogenesis, they can be also used as biomaterials for promoting tissue regeneration. Collectively, hydrogel-based tissue engineering toolkits will be useful for studying structure and function of vasculature in the tissue.