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New neurons in the injured brain actively interact with activated astrocytes to migrate efficiently toward the injured area
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Abstracts / Neuroscience Research 71S (2011) e46–e107
role. Our findings call for a redefinition of the functional role of lateral FPC in human cognition. Research fund: KAKENHI-19700312. doi:10.1016/j.neures.2011.07.313
O3-F-1-1 New neurons in the injured brain actively interact with activated astrocytes to migrate efficiently toward the injured area Naoko Kaneko 1 , Jane Y. Wu 2 , Marc Tessier-Lavigne 3 , Kazunobu Sawamoto 1 1
Dep. of Developmental and Regenerative Biol., Nagoya City University, Grad. Sch. of Med. Sci. 2 Dep. of Neurol. and Center for Genetic Med., Northwestern University Feinberg Sch. of Med. 3 Genentech In the adult brain, new neurons are continuously generated in the subventricular zone (SVZ), which migrate into the olfactory bulb and mature as functional neurons. We previously demonstrated that the migrating new neurons actively interact with the surrounding astrocytes by secreting the diffusible protein Slit1 to maintain their own migratory path. After ischemic injury, SVZ new neurons migrate toward the infarct area, where they regenerate a small number of neurons. During migration in the injured brain, the new neurons are closely associated with activated astrocytes. The mechanism regulating the interaction between new neurons and reactive astrocytes has been unknown. We found that the activated astrocytes strongly express a Slit receptor, Robo2. In the Slit1-deficient mice after ischemic injury, the number of migrating new neurons toward the injured area was significantly reduced. These new neurons were observed to be abnormally interacted with surrounding activated astrocytes. Similar migratory defects in the Slit1-deficient new neurons were observed when they were implanted into the wild-type brains after ischemic injury. These results suggest that the Slit-Robo mediated interaction between the new neurons and activated astrocytes regulates neuronal migration in the neuronal regeneration process after ischemic injury. Research fund: Grant-in-Aid for Young Scientists (B) (20700337). doi:10.1016/j.neures.2011.07.314
O3-F-1-2 The role of microRNAs in mammalian axon regeneration and presynapse formation Vivian Y. Poon , Emmanuel Beillard, Mathijs Voorhoeve, Marc L. Fivaz Duke-NUS Graduate Medical School The importance of microRNAs (miRNAs) in brain development is highlighted by the severe defects observed when miRNA biogenesis is disrupted in model systems like mice and zebrafish. Several miRNAs have been implicated in neuronal fate specification, patterning, neurogenesis, postsynaptic function, and neuronal activity. However, a large number of brain-specific and brainenriched miRNAs remain uncharacterized. To identify miRNAs important for axon differentiation and regeneration, I have compiled a list of miRNAs that are enriched in the developing mammalian brain. Using the rat adrenocarcinoma cell line PC12, which extends neurites when induced with nerve growth factor (NGF), I isolated miRNAs important for neurite outgrowth. Overexpression of miR-181a increased neurite outgrowth in PC12 cells and this effect was abolished with the disruption of the stem loop of pre-miR-181a. On the other hand, addition of a short hairpin inhibitor targeted against miR-181a led to decreased neurite outgrowth. I am currently testing the effect of overexpressing or knocking down miR-181a in primary hippocampal neurons. I have also developed a microfluidics-based imaging assay where I can study regeneration upon axotomy of primary neurons. I will examine if miRNAs that regulate axon growth also affect regeneration. As the role of miRNAs in presynapse formation has yet to be explored, I am also developing assays to study the role of miRNAs in this process. By expressing synaptogenic cues like netrin-G-ligand 3 (NGL-3) in HEK293T cells and co-culturing them with primary neurons, I am able to robustly induce presynapse formation as early as 4DIV. Using this sensitized early synapse-induction assay, I will overexpress or knock down miRNAs and observe the effects on presynapse formation. doi:10.1016/j.neures.2011.07.315
O3-F-1-3 Dendritic mRNA transport and local translation are responsible for the formation of neuronal networks Nobuyuki Shiina 1,2 , Makio Tokunaga 3,4 1 Okazaki Institute for Integrative Bioscience and National Institute for Basic Biology, Okazaki, Japan 2 Department of Basic Biology, SOKENDAI, Okazaki, Japan 3 Department of Biological Information, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama, Japan 4 Research Center for Allergy and Immunology, RIKEN, Yokohama, Japan
mRNA transport and subsequent local translation in dendrites play important roles in activity-dependent synaptic modification, consequently in long-term learning and memory. It is known that RNA granule, which is a macromolecular complex containing mRNAs, ribosomes and translation factors, plays central roles in mRNA transport and local control of translation in neuronal dendrites. RNG105 (RNA granule protein 105) is an RNA-binding protein that is localized to RNA granules in neurons. We generated RNG105-knockout mice and found that the transport of RNG105-associated mRNAs was reduced in dendrites of the knockout neurons, suggesting that RNG105 is responsible for the transport of mRNAs to dendrites. In RNG105 knockout neurons, dendritic arborization was impaired and synaptic contacts on dendrites were reduced, which resulted in the formation of poor neuronal networks. RNA interference of RNG105, as well as RNG140, a paralog of RNG105, also impaired dendritic arborization and synaptic contacts on dendrites although RNG105 and RNG140 appeared to function through distinct pathways. We propose that RNG105, and probably RNG140, participate in the dendritic transport of mRNAs to regulate the development and maintenance of functional neural networks. Research fund: KAKENHI 20022042. doi:10.1016/j.neures.2011.07.316
O3-F-2-1 Neurovascular niche in the ventricular zone of the adult zebrafish telencephalon Norihito Kishimoto 1,2 , Kohei Shimizu 1 , Hideto Nagai 1 , Kazuhide Asakawa 3 , Akihiro Urasaki 3 , Holger Knaut 4 , Shigenori Nonaka 5 , Koichi Kawakami 3 , Kazunobu Sawamoto 1 1 Dept. of Dev. and Regene. Biol., Nagoya City University Grad. Sch. of Med. Sci., Nagoya, Japan 2 Center for Integrated Medical Research, Keio University 3 Division of Molecular and Developmental Biology, National Institute of Genetics, Department of Genetics, Graduate University for Advanced Studies (SOKENDAI) 4 NYU School of Medicine 5 Laboratory for Spatiotemporal Regulation, National Institute for Basic Biology
In the adult mammalian brain, newborn cells generated in the subventricular zone migrate towards the olfactory bulb (OB) through the rostral migratory stream (RMS). We have previously reported that adult zebrafish also possesses a niche for neural stem cells in the telencephalic ventricular zone (TVZ), in which neuronal precursor cells (NPCs) are generated and migrate into the OB via the RMS. However, the cellular and molecular mechanisms underlying the formation of such structure and migration of these NPCs in the migratory stream remain uncovered. Here, we show that blood vessels precisely outline the migratory stream of the NPCs in the adult zebrafish brain. In this region, NPCs migrate along the blood vessels into the OB. In addition, we show that Sdf1 and Cxcr4 are expressed in the blood vessels and NPCs in the TVZ, respectively. We found that perturbation of the Sdf1/Cxcr4 signaling resulted in the dispersion of NPCs from the migratory stream without affecting cell proliferation in the TVZ, eventually leading to the decreased number of mature neurons in the OB. Thus, our data suggest that the Sdf1/Cxcr4 chemokine signaling plays an important role in the neurovascular niche to maintain the RMS structure within the adult zebrafish TVZ for the migration of NPCs to the OB. doi:10.1016/j.neures.2011.07.317
O3-F-2-2 The disruption of postnatal neurogenesis causes prepulse inhibition deficit at adulthood: A model for psychosis onset during adolescence in mice Nan-nan Guo , Fumikazu Suto, Noriko Osumi Division of Developmental Neuroscience, Tohoku University Graduate School of Medicine, Sendai, Japan Adolescence is the gradual and critical period of transition from childhood to adulthood. It is doubted that ablation of neurogenesis during this critical phase may be a risk factor for neuropsychiatric disorders such as
Abstracts / Neuroscience Research 71S (2011) e46–e107
role. Our findings call for a redefinition of the functional role of lateral FPC in human cognition. Research fund: KAKENHI-19700312. doi:10.1016/j.neures.2011.07.313
O3-F-1-1 New neurons in the injured brain actively interact with activated astrocytes to migrate efficiently toward the injured area Naoko Kaneko 1 , Jane Y. Wu 2 , Marc Tessier-Lavigne 3 , Kazunobu Sawamoto 1 1
Dep. of Developmental and Regenerative Biol., Nagoya City University, Grad. Sch. of Med. Sci. 2 Dep. of Neurol. and Center for Genetic Med., Northwestern University Feinberg Sch. of Med. 3 Genentech In the adult brain, new neurons are continuously generated in the subventricular zone (SVZ), which migrate into the olfactory bulb and mature as functional neurons. We previously demonstrated that the migrating new neurons actively interact with the surrounding astrocytes by secreting the diffusible protein Slit1 to maintain their own migratory path. After ischemic injury, SVZ new neurons migrate toward the infarct area, where they regenerate a small number of neurons. During migration in the injured brain, the new neurons are closely associated with activated astrocytes. The mechanism regulating the interaction between new neurons and reactive astrocytes has been unknown. We found that the activated astrocytes strongly express a Slit receptor, Robo2. In the Slit1-deficient mice after ischemic injury, the number of migrating new neurons toward the injured area was significantly reduced. These new neurons were observed to be abnormally interacted with surrounding activated astrocytes. Similar migratory defects in the Slit1-deficient new neurons were observed when they were implanted into the wild-type brains after ischemic injury. These results suggest that the Slit-Robo mediated interaction between the new neurons and activated astrocytes regulates neuronal migration in the neuronal regeneration process after ischemic injury. Research fund: Grant-in-Aid for Young Scientists (B) (20700337). doi:10.1016/j.neures.2011.07.314
O3-F-1-2 The role of microRNAs in mammalian axon regeneration and presynapse formation Vivian Y. Poon , Emmanuel Beillard, Mathijs Voorhoeve, Marc L. Fivaz Duke-NUS Graduate Medical School The importance of microRNAs (miRNAs) in brain development is highlighted by the severe defects observed when miRNA biogenesis is disrupted in model systems like mice and zebrafish. Several miRNAs have been implicated in neuronal fate specification, patterning, neurogenesis, postsynaptic function, and neuronal activity. However, a large number of brain-specific and brainenriched miRNAs remain uncharacterized. To identify miRNAs important for axon differentiation and regeneration, I have compiled a list of miRNAs that are enriched in the developing mammalian brain. Using the rat adrenocarcinoma cell line PC12, which extends neurites when induced with nerve growth factor (NGF), I isolated miRNAs important for neurite outgrowth. Overexpression of miR-181a increased neurite outgrowth in PC12 cells and this effect was abolished with the disruption of the stem loop of pre-miR-181a. On the other hand, addition of a short hairpin inhibitor targeted against miR-181a led to decreased neurite outgrowth. I am currently testing the effect of overexpressing or knocking down miR-181a in primary hippocampal neurons. I have also developed a microfluidics-based imaging assay where I can study regeneration upon axotomy of primary neurons. I will examine if miRNAs that regulate axon growth also affect regeneration. As the role of miRNAs in presynapse formation has yet to be explored, I am also developing assays to study the role of miRNAs in this process. By expressing synaptogenic cues like netrin-G-ligand 3 (NGL-3) in HEK293T cells and co-culturing them with primary neurons, I am able to robustly induce presynapse formation as early as 4DIV. Using this sensitized early synapse-induction assay, I will overexpress or knock down miRNAs and observe the effects on presynapse formation. doi:10.1016/j.neures.2011.07.315
O3-F-1-3 Dendritic mRNA transport and local translation are responsible for the formation of neuronal networks Nobuyuki Shiina 1,2 , Makio Tokunaga 3,4 1 Okazaki Institute for Integrative Bioscience and National Institute for Basic Biology, Okazaki, Japan 2 Department of Basic Biology, SOKENDAI, Okazaki, Japan 3 Department of Biological Information, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama, Japan 4 Research Center for Allergy and Immunology, RIKEN, Yokohama, Japan
mRNA transport and subsequent local translation in dendrites play important roles in activity-dependent synaptic modification, consequently in long-term learning and memory. It is known that RNA granule, which is a macromolecular complex containing mRNAs, ribosomes and translation factors, plays central roles in mRNA transport and local control of translation in neuronal dendrites. RNG105 (RNA granule protein 105) is an RNA-binding protein that is localized to RNA granules in neurons. We generated RNG105-knockout mice and found that the transport of RNG105-associated mRNAs was reduced in dendrites of the knockout neurons, suggesting that RNG105 is responsible for the transport of mRNAs to dendrites. In RNG105 knockout neurons, dendritic arborization was impaired and synaptic contacts on dendrites were reduced, which resulted in the formation of poor neuronal networks. RNA interference of RNG105, as well as RNG140, a paralog of RNG105, also impaired dendritic arborization and synaptic contacts on dendrites although RNG105 and RNG140 appeared to function through distinct pathways. We propose that RNG105, and probably RNG140, participate in the dendritic transport of mRNAs to regulate the development and maintenance of functional neural networks. Research fund: KAKENHI 20022042. doi:10.1016/j.neures.2011.07.316
O3-F-2-1 Neurovascular niche in the ventricular zone of the adult zebrafish telencephalon Norihito Kishimoto 1,2 , Kohei Shimizu 1 , Hideto Nagai 1 , Kazuhide Asakawa 3 , Akihiro Urasaki 3 , Holger Knaut 4 , Shigenori Nonaka 5 , Koichi Kawakami 3 , Kazunobu Sawamoto 1 1 Dept. of Dev. and Regene. Biol., Nagoya City University Grad. Sch. of Med. Sci., Nagoya, Japan 2 Center for Integrated Medical Research, Keio University 3 Division of Molecular and Developmental Biology, National Institute of Genetics, Department of Genetics, Graduate University for Advanced Studies (SOKENDAI) 4 NYU School of Medicine 5 Laboratory for Spatiotemporal Regulation, National Institute for Basic Biology
In the adult mammalian brain, newborn cells generated in the subventricular zone migrate towards the olfactory bulb (OB) through the rostral migratory stream (RMS). We have previously reported that adult zebrafish also possesses a niche for neural stem cells in the telencephalic ventricular zone (TVZ), in which neuronal precursor cells (NPCs) are generated and migrate into the OB via the RMS. However, the cellular and molecular mechanisms underlying the formation of such structure and migration of these NPCs in the migratory stream remain uncovered. Here, we show that blood vessels precisely outline the migratory stream of the NPCs in the adult zebrafish brain. In this region, NPCs migrate along the blood vessels into the OB. In addition, we show that Sdf1 and Cxcr4 are expressed in the blood vessels and NPCs in the TVZ, respectively. We found that perturbation of the Sdf1/Cxcr4 signaling resulted in the dispersion of NPCs from the migratory stream without affecting cell proliferation in the TVZ, eventually leading to the decreased number of mature neurons in the OB. Thus, our data suggest that the Sdf1/Cxcr4 chemokine signaling plays an important role in the neurovascular niche to maintain the RMS structure within the adult zebrafish TVZ for the migration of NPCs to the OB. doi:10.1016/j.neures.2011.07.317
O3-F-2-2 The disruption of postnatal neurogenesis causes prepulse inhibition deficit at adulthood: A model for psychosis onset during adolescence in mice Nan-nan Guo , Fumikazu Suto, Noriko Osumi Division of Developmental Neuroscience, Tohoku University Graduate School of Medicine, Sendai, Japan Adolescence is the gradual and critical period of transition from childhood to adulthood. It is doubted that ablation of neurogenesis during this critical phase may be a risk factor for neuropsychiatric disorders such as