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Glutamate transporter GLAST is essential for cytodifferentiation of Bergmann glia and maintenance of excitatory synaptic wiring in the cerebellum
| Content Provider | Semantic Scholar |
|---|---|
| Author | Miyazaki, Taisuke Yamasaki, Miwako Hashimoto, Kouichi Shimamoto, Keiko Watanabe, Masahiko |
| Copyright Year | 2011 |
| Abstract | s / Neuroscience Research 71S (2011) e46–e107 e63 a recently found neuropeptide QRFP in this signaling. We found that QRFP−/− mice were lean due to hypophagia. Orexigenic effect induced by central administration of ghrelin was almost completely deficient in the QRFP−/− mice. QRFP neurons received rich projections from NPY/AgRP/GABA neurons in the arcuate nucleus, and excited by GABA. Immunohistochemical analysis revealed existence of QRFP-immunoreactive fibers in the nucleus accumbens, where QRFP receptor was highly expressed. QRFP evoked a potent orexigenic effect when microinjected into the nucleus accumbens. These observations suggest that QRFP is an important mediator that conveys information gathered in the hypothalamus to the nucleus accumbens to evoke feeding behavior. Research fund: ERATO Yanagisawa Orphan Receptor Project, KAKENHI. doi:10.1016/j.neures.2011.07.265 O3-B-1-1 Glutamate transporter GLAST is essential for cytodifferentiation of Bergmann glia and maintenance of excitatory synaptic wiring in the cerebellum Taisuke Miyazaki 1 , Miwako Yamasaki 1, Kouichi Hashimoto 2,3, Keiko Shimamoto 4, Kazuhisa Kohda 5, Michisuke Yuzaki 5, Kohichi Tanaka 6, Masanobu Kano 2, Masahiko Watanabe 1 1 Dept. Anat., Grad. Sch. of Med., Hokkaido Univ., Sapporo, Japan 2 Dept. Neurophysiol., Grad. Sch. Med., Tokyo Univ., Tokyo, Japan 3 Dept. Neurophysiol., Grad. Sch. Biomed. Sci., Hiroshima Univ., Higashi-Hiroshima, Japan 4 Suntory Foundation for Life Sciences, Osaka, Japan 5 Dept. Physiol., Sch. Med., Keio Univ., Tokyo, Japan 6 Dept. Mol. Neurosci., Sch. Biomed. Sci., Tokyo Med. Dent. Univ., Tokyo, Japan Plasmalemmal glutamate transporters are involved in rapid clearance of synaptically-released glutamate. In the cerebellum, glutamate transporter GLAST is abundantly expressed in Bergmann glia (BG) and plays a critical role in maintaining functional one-to-one relationship in synaptic transmission between climbing fibers (CFs) and Purkinje cells (PCs). In this study, we examined its role in the development and maintenance of cerebellar neural circuits. In GLAST-KO mice, BG processes began to retract from PC spines and dendrites during the synaptogenic period. The impaired glial coverage was progressively exacerbated with maturation, causing a significant fraction of synapses and dendrites uncovered with BG processes in the adult. A week of chronic application of PMB-TBOA, a specific blocker of glial glutamate transporters, to adult cerebellum caused a similar defect, suggesting that activity of glial transporter is required to maintain the ensheathment by BG. CF-innervation of PCs almost normally developed during the first and second postnatal weeks, but aberrant multiple CF innervation became evident thereafter. The aberrant innervation was caused by intrusion of main ascending branches and the thin transverse collaterals into nearby PC dendrites. Furthermore, ectopic parallel fiber (PF) synapses were also observed at proximal PC dendrites. These results suggest that BG processes equipped with GLAST act as both functional and physical insulators essential for the maintenance of proper innervation territory by PFs at distal dendrites and by single CFs at proximal dendrites. Research fund: CREST. doi:10.1016/j.neures.2011.07.266 O3-B-1-2 The role of prospero/prox1, a determinant of glial cell fate, in Caenorhabditis elegans Eriko Kage-Nakadai , Shohei Mitani Dept. Physiol., Tokyo Women's Med. Univ. Sch. Med., Tokyo, Japan Glia is a major population of cells in the vertebrate brain. Recently, glial roles in diverse neural processes have been disclosed. C. elegans nervous system contains 302 neurons and 56 glia-like cells. Only a few aspects of C. elegans glia-like cells have been characterized, so far, although simple and transparent worm nervous system seems to be an ideal model for analyzing glia or neuron-glia interaction. To better characterize glial development and function of C. elegans model, we first searched genes selectively expressed in C. elegans glia-like cells. As a result, we found that C. elegans homolog of HMIT, which encodes H+/myoinositol transporter and is one of the glial markers known in mammals, was expressed in a subset of glia, called amphid and phasmid sheath glia. Next we performed RNAi screening for transcription factors that regulate the expression of HMIT using transgenic reporter worms. We successfully identified ceh-26, which encodes C. elegans homolog of Drosophila prospero/mammalian prox1, as a positive regulator. Prospero/Prox1 is a homeodomain transcription factor required for the early determination of glia and lymphatic endothelial cells. The expression of CEH-26::EGFP fusion protein revealed that CEH-26 was localized in nuclei of the glia and the excretory canal cell, an fluid regulatory organ in C. elegans. These results suggest that mammalian and C. elegans glia share, at least to some extent, common features and developmental mechanisms. Because ceh-26 mutant worms are lethal due to dysfunction of the excretory canal cell, we are analyzing glia-specific ceh-26 KO worms to reveal glial differentiation and function. Research fund: This work was supported by the Kato Memorial Bioscience Foundation. doi:10.1016/j.neures.2011.07.267 O3-B-1-3 The molecular mechanism of histamine uptake by human astrocytoma-derived cell line Fumito Naganuma , Takeo Yoshikawa, Tadaho Nakamura, Toshie Idutsu, Kazuhiko Yanai Dept. Pharmacol., Tohoku Univ., Sendai Brain histamine has been characterized as a neurotransmitter and implicated in a variety of biological events including sleep-wake cycle, learning and emotion. The inactivation of histamine is one of the essential processes to maintain the histaminergic neuronal activities. Previous studies using rodents have shown that histamine was mainly transported and metabolized in astrocytes. However, the precise molecular mechanism of histamine transport into human astrocytes remained to be elucidated. This study aims to elucidate mechanism of histamine uptake in human astrocytes. We first examined histamine uptake in human astrocytoma-derived cell lines, 1321N1 and U251MG cells. Histamine was taken up into both cell lines in a dose-dependent manner, suggesting that human astrocytes as well as rodents participate in histamine clearance. Next, we performed RT-PCR analyses to determine which cation transporters are expressed. Surprisingly, organic cation transporter 3 (OCT3), which is now assumed to responsible for histamine uptake in rodent astrocytes, was not expressed. On the other hand, plasma membrane monoamine transporter (PMAT), which is a high-capacity and a low-specificity transporter for various neurotransmitters such as dopamine and serotonin, was highly expressed in both human cell lines. Finally, we examined the role of PMAT in histamine transport by using gene-silencing technology. The siRNA against PMAT dramatically inhibited histamine uptake into 1321N1 cells. The present study is the first to reveal that PMAT, but not OCT3, was highly expressed in human astrocytomaderived cell lines and the PMAT knockdown in 1321N1 cells led to a reduced histamine uptake. Our data therefore suggest the predominant role of PMAT in histamine uptake by human astrocytes. Further studies are needed to reveal the exact molecular mechanism for histamine uptake in the human brain. doi:10.1016/j.neures.2011.07.268 O3-B-1-4 Expression of FABP7 in normal and injured brain cortex and its role in astrocyte proliferation Kazem Sharifi 1 , Yusuke Morihiro 2, Yuki Yasumoto 1, Motoko Maekawa 3, Majid Ebrahimi 1, Nobuko Tokuda 1, Takeo Yoshikawa 3, Yuji Owada 1 1 Dep. of Organ. Anat., Grad. Sch. of Med., Yamaguchi Univ., Ube, Japan 2 Dep. of Neurosurg., Grad. Sch. of Med., Yamaguchi Univ., Ube, Japan 3 Dep. of Mol. Psych., RIKEN Brain Sci. Inst., Wako, Japan The glial scar formation (reactive gliosis), in which astrocytes as well as other types of gilal cells undergo massive proliferation, is a common hallmark of all brain pathologies. Brain-type fatty acid binding protein (FABP7) is abundantly expressed in neural stem cells and astrocytes of developing brain, suggesting its role in differentiation and/or proliferation of glial cells through regulation of lipid metabolism and/or signaling. However, the role of FABP7 in proliferation of glial cells during reactive gliosis is unknown. In this study, we examined the expression of FABP7 in mouse cortical stab injury model and also the phenotype of FABP7 KO mice in glial cell proliferation. In Western blot, FABP7 expression was increased significantly in the injured cortex compared to the contralateral side. In immunohistochemistry on normal cortex, FABP7 was localized to GFAP+ astrocytes (21% of FABP7+ cells) and NG2+ polydendrocytes (62%). In the injured cortex, the population of FABP7+NG2+ cells did not show any significant change, but that of FABP7+GFAP+ cells increased significantly (approx. 6 fold). In stab injured cortex of FABP7 KO mice, a decrease in total number of reactive astrocytes and in the number of BrdU+ astrocytes was detected compared with wild type mice. Furthermore, the primary cultured astrocytes from FABP7 null mice showed a significant decrease in their proliferation and in their omega-3 fatty acid incorporation compared to wild type, when assessed by BrdU incorpora- |
| File Format | PDF HTM / HTML |
| Volume Number | 71 |
| Alternate Webpage(s) | https://api.elsevier.com/content/article/pii/S0168010211004494 |
| Alternate Webpage(s) | https://www.sciencedirect.com/science/article/pii/S0168010211004494?dgcid=api_sd_search-api-endpoint |
| Alternate Webpage(s) | https://doi.org/10.1016/j.neures.2011.07.266 |
| Journal | Neuroscience Research |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
