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Regional differences in proliferation and maturation of neural progenitors in the adult mouse hippocampus: A stereology-based study
S102
Abstracts
In the present study, we attempt to induce differentiation of cholinergic neurons by forced expression of some genes responsible for differentiation of cholinergic neurons during the embryonic stage. doi:10.1016/j.neures.2009.09.445
P1-f28 Histochemical analysis of two neurogenic regions in the adult ferret brain Yasuharu Takamori 1 , Taketoshi Wakabayashi 1 , Tetsuji Mori 1 , Kotaro Kitaya 1 , Jun Kosaka 2 , Hisao Yamada 1 1 Department Anatomy and Cell Science, Kansai Medical University, Osaka, Japan; 2 Department Cytology and Histology, Okayama Uinversity Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
In the adult mammalian brain, two neurogenic regions are characterized, the subgranular zone of the dentate gyrus and the subventricular zone of the lateral ventricle. These regions were first identified in rodents, such as mouse and rat, and later examined in other mammalian species, including rabbit, monkey and human, but not well understood in carnivore. Thus, we try to investigate the location, architecture and cellular composition of two neurogenic regions in adult ferret, which is a well-used carnivore as a model animal. Adult ferrets were perfused with fixative containing 4% formaldehyde, and coronal or sagittal sections were prepared. We immunohistochemically analyzed using antibodies against several cell-type specific markers, GFAP or vimentin as neural stem cells, PSA-NCAM or doublecortin as neuronal progenitor cells and NeuN as mature neurons, and compared with previously reported mammalian species. doi:10.1016/j.neures.2009.09.446
P1-f29 Cellular aspects of the brain dopaminergic neurogenesis in planarians Kaneyasu Nishimura 1 , Takeshi Inoue 1 , Yoshihisa Kitamura 2 , Kanji Yoshimoto 3 , Hiroshi Ikegaya 3 , Takashi Taniguchi 2 , Kiyokazu Agata 1 1
Department Biophys., Grad. Sch. Sci., Kyoto University, Kyoto, Japan; Department Neurobiol., Kyoto Pharm. University, Kyoto, Japan; 3 Department Legal Med., Kyoto Pref. University Med., Kyoto, Japan 2
Although it is well known that planarians can spontaneously reconstruct their brain after amputation, there are still no observations that neurogenesis occurs in the planarian brain. Here we show the cellular events of dopamine (DA) neurogenesis in the brain after injury by 6-hydroxydopamine (6-OHDA), a DA neurotoxin. Selective DA neural degeneration was induced in the brain within 1 day after 6-OHDA injury. Thereafter, newly formed DA neurons were appeared from 5 days after 6-OHDA injury, and then increased for several days. BrdU-incorporation was also detected in newly formed DA neurons. Moreover, newly formed DA neurons were distributed at approximately the same locations as the original DA neurons in the brain. These results revealed that there are mechanisms for supporting spontaneously DA neurogenesis in the brain. doi:10.1016/j.neures.2009.09.447
P1-f30 The tumor suppressor Adenomatous Polyposis Coli regulates adult neurogenesis Tetsuya Imura 1 , Xiao-hang Wang 1 , Tetsuo Noda 2 , Sofroniew Michael 3 , Shinji Fushiki 1 1
Department of Pathology and Applied Neurobiology, Kyoto Prefectural University of Medicine, Kyoto, Japan; 2 Department of Cell Biology, Cancer Institute, Tokyo, Japan; 3 Department of Neurobiology, UCLA, Los Angeles, USA The tumor suppressor Adenomatous Polyposis Coli (APC) is highly expressed in the adult central nervous system (CNS), but the function of APC in neural cells remains largely unknown. To study the roles of APC in adult neurogenesis, we applied a conditional gene targeting strategy to delete the APC gene in adult neural stem cells and their progeny. The deletion of APC in adult neural stem cells results in the marked nuclear accumulation of b-catenin, demonstrating that APC is an important regulator of the Wnt/b-catenin pathway in adult neural stem cells. APC-conditional knockout mice exhibit small olfactory bulbs with the shrunken granule cell layer. Adult olfactory neurogenesis is markedly reduced, which is likely due to the aberrant migration and maturation of neuroblasts. Thus, APC plays an important role in neuronal differentiation and migratory behavior of newly generated neurons. doi:10.1016/j.neures.2009.09.448
P1-f31 Regional differences in proliferation and maturation of neural progenitors in the adult mouse hippocampus: A stereology-based study Shozo Jinno, Toshio Kosaka Department of Anatomy & Neurobiology, Grad. Sch. of Medical Sciences, Kyushu University, Fukuoka, Japan The dentate gyrus of the hippocampus shows continuous neurogenesis during adult life in mammals, including humans. Importantly, several lines of evidence suggest that adult hippocampal neurogenesis is associated with various psychiatric disorders, such as depression, epilepsy and schizophrenia. However, basic questions about the differential regulation of neurogenesis within regions of the dentate gyrus have been largely unexplored. Here, we show the regional differences in proliferation and maturation of neural progenitors in the adult mouse hippocampus using immunocytochemical markers. Proliferation is identified by Ki-67. Stages of adult neurogenesis are determined by the combination of multiple markers, such as BLBP, doublecortin, calretinin and NeuN. The numerical densities of cells expressing above markers are stereologically estimated along the dorsoventral and transverse axes. The present results provide an anatomical basis to know the regulation of neurogenesis in the adult hippocampus. doi:10.1016/j.neures.2009.09.449
P1-f32 A possible new site for adult neurogenesis: GABA-neuron production in the parenchyma of the cerebral cortex of adult mice Shogo Ninomiya 1 , Tetsufumi Itou 2 , Chiyoko Tanahira 1 , Kaoru Akashi 3 , Kenji Sakimura 3 , Nobuaki Tamamaki 1 1 Department of Morphological Neural Science, Graduate School of Medical Sciences, Kumamoto University, Japan; 2 Department of Anatomy, Faculty of Medical Sciences, University of Fukui, Japan; 3 Department of Cellular Neurobiology, Brain Research Institute, Niigata University, Japan
In embryonic stages, the neural stem cells reside in the ventricular zone (VZ) and give rise to neurons or intermediate progenitors for neurogenesis in the subventricular zone (SVZ). Recently, however, the marginal zone of the embryonic telencephalon was suggested as another site for neurogenesis (J. Neurosci., 27:11376). In this study we have investigated if GABAergic neurons are produced in the adult mouse cerebral cortex. We induced epilepsy in the mice which were obtained by mating GAD67-Cre knock-in mouse or PV-Cre BAC-transgenic mouse with GFP Cre-reporter mouse, and then found GFP-positive cells incorporating BrdU and expressing cell-cycle markers in the cerebral cortex. We speculated that epilepsy enhanced neurogenesis in the cerebral cortex to the level we can detect by routine method. doi:10.1016/j.neures.2009.09.450
P1-f33 Change in the radiosensitivity of developing neurons in adult rat brain Tomoaki Shirao 1 , Yoshihisa Mizukami 1 , Kenji Hanamura 1 , Yukari Yoshida 2 , Yoshiyuki Suzuki 2 , Takashi Nakano 2 , Nobuhiko Kojima 1 1
Department Neurobiol.&Behav., Gunma University Grad. Sch. of Med., Maebashi, Japan; 2 Heavy Ion Med. Cent., Gunma University, Maebashi, Japan Developmental change in the radiosensitivity of newly-generated neurons in adult brain has not been studied although adult neuronal generation itself is sensitive to x-irradiation. In this study, we examined the radiosensitivity of newly generated neurons in the state of migration and maturation by detecting the localization of doublecortin and drebrin E in the pathway from the subventricular zone (SVZ) to the olfactory bulb (OB). Two days after 10 Gy x-irradiation to rat brain, we confirmed the disappearance of the migrating cells in the SVZ. In the core of the OB, in which neurons are still migrating, the neurons were greatly reduced after x-irradiation. In contrast, in the granule cell layer of the OB, in which large part of newly-generated neurons stop migrating, the young neurons were preserved after x-irradiation. Therefore, in the SVZ-OB system, the migrating neurons are more sensitive to x-irradiation in compared with more maturating postmigratory young neurons. doi:10.1016/j.neures.2009.09.451
Abstracts
In the present study, we attempt to induce differentiation of cholinergic neurons by forced expression of some genes responsible for differentiation of cholinergic neurons during the embryonic stage. doi:10.1016/j.neures.2009.09.445
P1-f28 Histochemical analysis of two neurogenic regions in the adult ferret brain Yasuharu Takamori 1 , Taketoshi Wakabayashi 1 , Tetsuji Mori 1 , Kotaro Kitaya 1 , Jun Kosaka 2 , Hisao Yamada 1 1 Department Anatomy and Cell Science, Kansai Medical University, Osaka, Japan; 2 Department Cytology and Histology, Okayama Uinversity Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
In the adult mammalian brain, two neurogenic regions are characterized, the subgranular zone of the dentate gyrus and the subventricular zone of the lateral ventricle. These regions were first identified in rodents, such as mouse and rat, and later examined in other mammalian species, including rabbit, monkey and human, but not well understood in carnivore. Thus, we try to investigate the location, architecture and cellular composition of two neurogenic regions in adult ferret, which is a well-used carnivore as a model animal. Adult ferrets were perfused with fixative containing 4% formaldehyde, and coronal or sagittal sections were prepared. We immunohistochemically analyzed using antibodies against several cell-type specific markers, GFAP or vimentin as neural stem cells, PSA-NCAM or doublecortin as neuronal progenitor cells and NeuN as mature neurons, and compared with previously reported mammalian species. doi:10.1016/j.neures.2009.09.446
P1-f29 Cellular aspects of the brain dopaminergic neurogenesis in planarians Kaneyasu Nishimura 1 , Takeshi Inoue 1 , Yoshihisa Kitamura 2 , Kanji Yoshimoto 3 , Hiroshi Ikegaya 3 , Takashi Taniguchi 2 , Kiyokazu Agata 1 1
Department Biophys., Grad. Sch. Sci., Kyoto University, Kyoto, Japan; Department Neurobiol., Kyoto Pharm. University, Kyoto, Japan; 3 Department Legal Med., Kyoto Pref. University Med., Kyoto, Japan 2
Although it is well known that planarians can spontaneously reconstruct their brain after amputation, there are still no observations that neurogenesis occurs in the planarian brain. Here we show the cellular events of dopamine (DA) neurogenesis in the brain after injury by 6-hydroxydopamine (6-OHDA), a DA neurotoxin. Selective DA neural degeneration was induced in the brain within 1 day after 6-OHDA injury. Thereafter, newly formed DA neurons were appeared from 5 days after 6-OHDA injury, and then increased for several days. BrdU-incorporation was also detected in newly formed DA neurons. Moreover, newly formed DA neurons were distributed at approximately the same locations as the original DA neurons in the brain. These results revealed that there are mechanisms for supporting spontaneously DA neurogenesis in the brain. doi:10.1016/j.neures.2009.09.447
P1-f30 The tumor suppressor Adenomatous Polyposis Coli regulates adult neurogenesis Tetsuya Imura 1 , Xiao-hang Wang 1 , Tetsuo Noda 2 , Sofroniew Michael 3 , Shinji Fushiki 1 1
Department of Pathology and Applied Neurobiology, Kyoto Prefectural University of Medicine, Kyoto, Japan; 2 Department of Cell Biology, Cancer Institute, Tokyo, Japan; 3 Department of Neurobiology, UCLA, Los Angeles, USA The tumor suppressor Adenomatous Polyposis Coli (APC) is highly expressed in the adult central nervous system (CNS), but the function of APC in neural cells remains largely unknown. To study the roles of APC in adult neurogenesis, we applied a conditional gene targeting strategy to delete the APC gene in adult neural stem cells and their progeny. The deletion of APC in adult neural stem cells results in the marked nuclear accumulation of b-catenin, demonstrating that APC is an important regulator of the Wnt/b-catenin pathway in adult neural stem cells. APC-conditional knockout mice exhibit small olfactory bulbs with the shrunken granule cell layer. Adult olfactory neurogenesis is markedly reduced, which is likely due to the aberrant migration and maturation of neuroblasts. Thus, APC plays an important role in neuronal differentiation and migratory behavior of newly generated neurons. doi:10.1016/j.neures.2009.09.448
P1-f31 Regional differences in proliferation and maturation of neural progenitors in the adult mouse hippocampus: A stereology-based study Shozo Jinno, Toshio Kosaka Department of Anatomy & Neurobiology, Grad. Sch. of Medical Sciences, Kyushu University, Fukuoka, Japan The dentate gyrus of the hippocampus shows continuous neurogenesis during adult life in mammals, including humans. Importantly, several lines of evidence suggest that adult hippocampal neurogenesis is associated with various psychiatric disorders, such as depression, epilepsy and schizophrenia. However, basic questions about the differential regulation of neurogenesis within regions of the dentate gyrus have been largely unexplored. Here, we show the regional differences in proliferation and maturation of neural progenitors in the adult mouse hippocampus using immunocytochemical markers. Proliferation is identified by Ki-67. Stages of adult neurogenesis are determined by the combination of multiple markers, such as BLBP, doublecortin, calretinin and NeuN. The numerical densities of cells expressing above markers are stereologically estimated along the dorsoventral and transverse axes. The present results provide an anatomical basis to know the regulation of neurogenesis in the adult hippocampus. doi:10.1016/j.neures.2009.09.449
P1-f32 A possible new site for adult neurogenesis: GABA-neuron production in the parenchyma of the cerebral cortex of adult mice Shogo Ninomiya 1 , Tetsufumi Itou 2 , Chiyoko Tanahira 1 , Kaoru Akashi 3 , Kenji Sakimura 3 , Nobuaki Tamamaki 1 1 Department of Morphological Neural Science, Graduate School of Medical Sciences, Kumamoto University, Japan; 2 Department of Anatomy, Faculty of Medical Sciences, University of Fukui, Japan; 3 Department of Cellular Neurobiology, Brain Research Institute, Niigata University, Japan
In embryonic stages, the neural stem cells reside in the ventricular zone (VZ) and give rise to neurons or intermediate progenitors for neurogenesis in the subventricular zone (SVZ). Recently, however, the marginal zone of the embryonic telencephalon was suggested as another site for neurogenesis (J. Neurosci., 27:11376). In this study we have investigated if GABAergic neurons are produced in the adult mouse cerebral cortex. We induced epilepsy in the mice which were obtained by mating GAD67-Cre knock-in mouse or PV-Cre BAC-transgenic mouse with GFP Cre-reporter mouse, and then found GFP-positive cells incorporating BrdU and expressing cell-cycle markers in the cerebral cortex. We speculated that epilepsy enhanced neurogenesis in the cerebral cortex to the level we can detect by routine method. doi:10.1016/j.neures.2009.09.450
P1-f33 Change in the radiosensitivity of developing neurons in adult rat brain Tomoaki Shirao 1 , Yoshihisa Mizukami 1 , Kenji Hanamura 1 , Yukari Yoshida 2 , Yoshiyuki Suzuki 2 , Takashi Nakano 2 , Nobuhiko Kojima 1 1
Department Neurobiol.&Behav., Gunma University Grad. Sch. of Med., Maebashi, Japan; 2 Heavy Ion Med. Cent., Gunma University, Maebashi, Japan Developmental change in the radiosensitivity of newly-generated neurons in adult brain has not been studied although adult neuronal generation itself is sensitive to x-irradiation. In this study, we examined the radiosensitivity of newly generated neurons in the state of migration and maturation by detecting the localization of doublecortin and drebrin E in the pathway from the subventricular zone (SVZ) to the olfactory bulb (OB). Two days after 10 Gy x-irradiation to rat brain, we confirmed the disappearance of the migrating cells in the SVZ. In the core of the OB, in which neurons are still migrating, the neurons were greatly reduced after x-irradiation. In contrast, in the granule cell layer of the OB, in which large part of newly-generated neurons stop migrating, the young neurons were preserved after x-irradiation. Therefore, in the SVZ-OB system, the migrating neurons are more sensitive to x-irradiation in compared with more maturating postmigratory young neurons. doi:10.1016/j.neures.2009.09.451