Oral Session

Oral Session 13 一般口演13

O13-1 Axonal domain components are transported independently in separate vesicles ランビエ絞輪局在分子の軸索輸送とランビエ絞輪形成 Bekku Yoko（別宮洋子），Salzer James New York University Neuroscience Institute The trafficking and targeting of proteins to distinct sites underlies the exquisite, polarized organization of neurons. Myelinated axons are further organized into a series of functionally and biochemically distinct domains, i.e. the nodes, paranodes, juxtaparanodes, and internodes. We previously reported that NF186 and other axonal CAMs redistribute to the node and to other domains from pre-existing pools of diffusely distributed proteins on the axon surface (Zhang et al., Neuron 2012). In contrast, ion channels and ankyrin G require transport to the node during myelination. The slow replenishment of all nodal components in mature myelinated fibers also depends on transport. We have now directly investigated how these proteins are transported within the axon prior to and after myelination by live imaging. In general, each nodal protein is anterogradely transported in separate vesicles except for NrCAM and NF186, which are co-transported in the same vesicles. Likewise, CAMs destined for other axonal domains are independently transported in distinct vesicles. In contrast, there is significant co-transport of retrogradely transported proteins likely reflecting recruitment into a common endocytic vesicle. These patterns of transport did not change with myelination. Moreover, endosomal transport was accelerated during myelination, consistent with active removal of nodal components from the internode. Taken together with our earlier study, these results support a model in which nodal component are sorted to separate vesicles and transported independently to the axon rather than as a preformed complex; upon myelination, they assemble at the node via a combination of local recruitment (CAMs) and de novo transport (channels and cytoskeletal proteins).		O13-2 The role of deficiency in glial ABCA1 on pathogenesis of glaucoma 緑内障発症におけるグリア細胞のABCA1の役割 Shinozaki Youichi（篠崎陽一）¹，行方和彦²，柏木賢治³，大野伸彦^4,5，武田明子¹，原田高幸² ¹Dept. Neuropharmacol., Interdiscp. Grad. Sch. Med., Univ. of Yamanashi, Yamanashi, JAPAN ²Vis. Res. Project, Tokyo Metr. Inst. Med. Sci., Tokyo, JAPAN ³Dept. Ophthalmol., Interdscp. Grad. Sch. Med., Univ. of Yamanashi, Yamanashi, JAPAN ⁴Dev. Neurobiol. Bioinfo., Natl. Inst. Physiol. Sci., Aichi, JAPAN ⁵Div. Anatomy, Jichi Med. Univ. Tochigi, JAPAN Glaucoma is second leading cause of blindness worldwide which is characterized by progressive degeneration of retinal ganglion cells (RGCs). Although it is difficult to focus on single candidate gene for pathogenesis because glaucoma is multifactorial disease, recent large scale genome wide association studies (GWAS) from three independent international cohorts have shown that single nucleotide polymorphism (SNP) of ABCA1 gene has the highest correlation for pathogenesis of glaucoma. The correlation between ABCA1 gene and glaucoma has clearly demonstrated, however, its causal relationship in glaucoma is still totally unrevealed. First, it is unclear whether or not ABCA1 affects intraocular pressure (IOP). Second, which of gain-of-neurotoxicity or loss-of-function of ABCA1 is involved in glaucoma. Third, which type of cells in the retina is dominantly expressing ABCA1. To clarify these points, we have analyzed conventional ABCA1 knockout (ABCA1KO) and glia-selective ABCA1 knockout (Glia-ABCA1cKO) mice. We found that Abca1 mRNA was highly enriched in retinal glial cells. ABCA1KO and Glia-ABCA1cKO mice showed no changes in IOP and apoptosis of RGCs at middle-age (12 months old). Associated with RGC damages, visual function estimated by multifocal electroretinogram showed clear reduction in middle-aged Glia-ABCA1cKO mice. Based on these findings, we concluded that (1) ABCA1 has no impact on IOP at least in the mice models; (2) loss-of-function of ABCA1 is involved in glaucoma; and (3) ABCA1 in glial cells has indispensable roles for pathogenesis of glaucoma.

O13-3 Role of CD38 in Cuprizone-induced Demyelination Cuprizone誘発性脱髄におけるCD38の役割 Roobon Jureepon，服部剛志，Nguyen Dinh，堀修 Dept. of Neuroanat, Med. Kanazawa Univ. CD38 is an ADP-rybosyl cyclase that is involved in a variety of cellular processes. We recently reported that CD38 played important roles in the development of glial cells. However, functional role of CD38 in glial cells in pathological condition was unclear. To investigate its role in demyelination, we employed cuprizone (CPZ)-induced demyelination model. After CPZ administration CD38 expression increased in astrocytes and microglia in the corpus callosum. CPZ-induced activation of glial cells and demyelination were robustly attenuated in CD38KO mice. By using in vitro culture system we found that CD38 regulates activation of astrocytes and microglia. Furthermore, deletion of CD38 increased NAD level in the brain, which caused decreased activation of glial cells. These results suggest that deletion of CD38 attenuates CPZ-induced demyelination by decreasing glial activation.