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REMOVED: Increased neurogenesis in the rat hippocampus and dentate gyrus after spreading depression
Abstracts / Int. J. Devl Neuroscience 47 (2015) 1–131
ISDN2014 0336
ISDN2014 0340
Increased neurogenesis in the rat hippocampus and dentate gyrus after spreading depression
In vitro pro-inflammatory phenotype of fetal brain microglia is potentiated by an in vivo pre-exposure to inflammation: A prospective study in ovine fetus near term
Mahmoud Lotfinia 1,2 1
Shefa Neuroscience Research Center, Tehran, Iran Shahid-Beheshti University of Medical Science, Tehran, Iran 2
Spreading depression (SD) known by transient loss of spontaneous and evoked neuronal activity and changes in ionic, metabolic and hemodynamic characteristics of the brain. Neuronal damage followed by SD, supposed to have a dramatic impression on SDderived pathologic conditions. We aimed to determine whether SD is able to stimulate persistent neurogenesis. Wistar rat (60–80 g) randomly chosen and 3 mol/L KCl injected for induction of SD. Four weeks after the first injection, all rats were decapitated and the brains removed. The density of mitotic cells, divided cells, and new neurons in the pyramidal cell layer of hippocampal CA1 and CA3 and granular cell layer of dentate gyrus was assessed. We also detect the DNA during the S phase using Bromodeoxyuridine (BrdU). A remarkable increase occurred in the number of BrdU-labeled cells in hippocampal region, detected by immunohistochemistry method. The density of mitotic cells, divided cells, and new neurons in hippocampal CA1 and CA3 and granular cell layer of dentate gyrus also increased. We conclude that Spreading depression potentiates to trigger persistent neurogenesis in rat hippocampus. http://dx.doi.org/10.1016/j.ijdevneu.2015.04.280 ISDN2014 0337 Snail coordinately regulates downstream pathways to control multiple aspects of mammalian neural precursor development Mark A. Zander 1,2,∗ , Sarah E. Burns 1 , Guang Yang 1 , David R. Kaplan 1,2,3 , Freda D. Miller 1,2,3,4 1 Neuroscience and Mental Health Program, Hospital for Sick Children, Toronto, Canada M5G 1L7 2 Institute for Medical Sciences, University of Toronto, Toronto, Canada M5G 1X5 3 Departments of Molecular Genetics, University of Toronto, Toronto, Canada M5G 1X5 4 Departments of Physiology, University of Toronto, Toronto, Canada M5G 1X5
The Snail transcription factor plays a key role in regulating diverse developmental processes, but is not thought to play a role in mammalian neural precursors. Here, we have examined radial glial precursor cells of the embryonic murine cortex and demonstrate that Snail regulates their survival, self-renewal and differentiation into intermediate progenitors and neurons via two distinct and separable target pathways. First, Snail promotes cell survival by antagonizing a p53-dependent death pathway, since coincident p53 knockdown rescues survival deficits caused by Snail knockdown. Second, we show that the cell cycle phosphatase Cdc25b is regulated by Snail in radial precursors, and that Cdc25b coexpression is sufficient to rescue the decreased radial precursor proliferation and differentiation observed upon Snail knockdown. Thus, Snail acts through p53 and Cdc25b to coordinately regulate multiple aspects of mammalian embryonic neural precursor biology. http://dx.doi.org/10.1016/j.ijdevneu.2015.04.281
103
M. Cao 1,∗ , L.D. Durosier 1 , P. Burns 2 , G. Fecteau 2 , A. Desrochers 2 , M.G. Frasch 1,3 1 Department of Obstetrics and Gynaecology, CHU Ste-Justine Research Centre, Faculty of Medicine, Université de Montréal, Montréal, QC, Canada 2 Department of Clinical Sciences, Faculty of Veterinary Medicine, Université de Montréal, St-Hyacinthe, QC, Canada 3 Animal Reproduction Research Centre (CRRA), Faculty of Veterinary Medicine, Université de Montréal, St-Hyacinthe, QC, Canada
Introduction: Neuroinflammation in utero may result in lifelong neurological deficits with microglia thought to play a key role. Double-hit experimental models of neuroinflammation are needed. We aimed to develop an in vivo – in vitro exposure model of neuroinflammation. Methods: Near-term ovine fetuses were surgically instrumented with arterial and venous catheters. At 0.89 gestation (∼35 weeks in humans), animals received either lipopolysaccharide (LPS group, n = 12) or saline (Control, n = 9) intravenously on experimental days 1 and 2. Fetal arterial blood samples were taken at baseline and selected time points post LPS for plasma cytokines ELISA (IL-1beta and IL-6). At 54 hours, the animals were euthanized. Brains from instrumented fetuses and twins (controls) were perfusion-fixed for immunohistochemical analysis of regional microglia counts. In addition, two cell cultures were derived from brains of in vivo LPS exposed group and six cultures from brains of in vivo controls. Microglia were cultured for 6 h with or without LPS. Microglia purity was verified immunocytochemically and by flow cytometry. Cell conditioned media were collected and IL-1beta was measured (ELISA). Results were considered significant if P < 0.05. Results: In vivo, IL-6, but not IL-1beta, peaked at 3 hours and declined to basal levels at 24 hours after the first LPS injection, with no further increase in IL-6 after the second LPS injection. LPS group showed higher regional microglia counts vs. controls. In vitro, at baseline, microglia secreted more IL-1beta in the in vivo LPS group than in Controls. LPS re-exposure further increased IL-1beta versus baseline. The relative IL-1beta increase was ∼4.6-fold in both cases. Discussion: Inflammatory microglial phenotype acquired during in vivo exposure to LPS is sustained and potentiated in vitro upon re-exposure to LPS. This model allows studying mechanisms of fetal neuroinflammation in utero and in vitro to identify potential therapeutic targets for early postnatal intervention. http://dx.doi.org/10.1016/j.ijdevneu.2015.04.282 ISDN2014 0341 Neuropsychological profile of children aged 5–7 years with Traumatic Brain Injury ˜ 1,∗ , Yulia Maria Jimena Sarmiento Bolanos Solovieva 2 , Luis Quintanar-Rojas 2 1 2
Universidades Federal de Paraná, Brazil Universidad Autonoma de Puebla, Mexico
Traumatic brain injury (TBI) is the leading cause of death among children and adolescents. The trauma in general is a real public health problem in any country in the world, with an upward trend
ISDN2014 0336
ISDN2014 0340
Increased neurogenesis in the rat hippocampus and dentate gyrus after spreading depression
In vitro pro-inflammatory phenotype of fetal brain microglia is potentiated by an in vivo pre-exposure to inflammation: A prospective study in ovine fetus near term
Mahmoud Lotfinia 1,2 1
Shefa Neuroscience Research Center, Tehran, Iran Shahid-Beheshti University of Medical Science, Tehran, Iran 2
Spreading depression (SD) known by transient loss of spontaneous and evoked neuronal activity and changes in ionic, metabolic and hemodynamic characteristics of the brain. Neuronal damage followed by SD, supposed to have a dramatic impression on SDderived pathologic conditions. We aimed to determine whether SD is able to stimulate persistent neurogenesis. Wistar rat (60–80 g) randomly chosen and 3 mol/L KCl injected for induction of SD. Four weeks after the first injection, all rats were decapitated and the brains removed. The density of mitotic cells, divided cells, and new neurons in the pyramidal cell layer of hippocampal CA1 and CA3 and granular cell layer of dentate gyrus was assessed. We also detect the DNA during the S phase using Bromodeoxyuridine (BrdU). A remarkable increase occurred in the number of BrdU-labeled cells in hippocampal region, detected by immunohistochemistry method. The density of mitotic cells, divided cells, and new neurons in hippocampal CA1 and CA3 and granular cell layer of dentate gyrus also increased. We conclude that Spreading depression potentiates to trigger persistent neurogenesis in rat hippocampus. http://dx.doi.org/10.1016/j.ijdevneu.2015.04.280 ISDN2014 0337 Snail coordinately regulates downstream pathways to control multiple aspects of mammalian neural precursor development Mark A. Zander 1,2,∗ , Sarah E. Burns 1 , Guang Yang 1 , David R. Kaplan 1,2,3 , Freda D. Miller 1,2,3,4 1 Neuroscience and Mental Health Program, Hospital for Sick Children, Toronto, Canada M5G 1L7 2 Institute for Medical Sciences, University of Toronto, Toronto, Canada M5G 1X5 3 Departments of Molecular Genetics, University of Toronto, Toronto, Canada M5G 1X5 4 Departments of Physiology, University of Toronto, Toronto, Canada M5G 1X5
The Snail transcription factor plays a key role in regulating diverse developmental processes, but is not thought to play a role in mammalian neural precursors. Here, we have examined radial glial precursor cells of the embryonic murine cortex and demonstrate that Snail regulates their survival, self-renewal and differentiation into intermediate progenitors and neurons via two distinct and separable target pathways. First, Snail promotes cell survival by antagonizing a p53-dependent death pathway, since coincident p53 knockdown rescues survival deficits caused by Snail knockdown. Second, we show that the cell cycle phosphatase Cdc25b is regulated by Snail in radial precursors, and that Cdc25b coexpression is sufficient to rescue the decreased radial precursor proliferation and differentiation observed upon Snail knockdown. Thus, Snail acts through p53 and Cdc25b to coordinately regulate multiple aspects of mammalian embryonic neural precursor biology. http://dx.doi.org/10.1016/j.ijdevneu.2015.04.281
103
M. Cao 1,∗ , L.D. Durosier 1 , P. Burns 2 , G. Fecteau 2 , A. Desrochers 2 , M.G. Frasch 1,3 1 Department of Obstetrics and Gynaecology, CHU Ste-Justine Research Centre, Faculty of Medicine, Université de Montréal, Montréal, QC, Canada 2 Department of Clinical Sciences, Faculty of Veterinary Medicine, Université de Montréal, St-Hyacinthe, QC, Canada 3 Animal Reproduction Research Centre (CRRA), Faculty of Veterinary Medicine, Université de Montréal, St-Hyacinthe, QC, Canada
Introduction: Neuroinflammation in utero may result in lifelong neurological deficits with microglia thought to play a key role. Double-hit experimental models of neuroinflammation are needed. We aimed to develop an in vivo – in vitro exposure model of neuroinflammation. Methods: Near-term ovine fetuses were surgically instrumented with arterial and venous catheters. At 0.89 gestation (∼35 weeks in humans), animals received either lipopolysaccharide (LPS group, n = 12) or saline (Control, n = 9) intravenously on experimental days 1 and 2. Fetal arterial blood samples were taken at baseline and selected time points post LPS for plasma cytokines ELISA (IL-1beta and IL-6). At 54 hours, the animals were euthanized. Brains from instrumented fetuses and twins (controls) were perfusion-fixed for immunohistochemical analysis of regional microglia counts. In addition, two cell cultures were derived from brains of in vivo LPS exposed group and six cultures from brains of in vivo controls. Microglia were cultured for 6 h with or without LPS. Microglia purity was verified immunocytochemically and by flow cytometry. Cell conditioned media were collected and IL-1beta was measured (ELISA). Results were considered significant if P < 0.05. Results: In vivo, IL-6, but not IL-1beta, peaked at 3 hours and declined to basal levels at 24 hours after the first LPS injection, with no further increase in IL-6 after the second LPS injection. LPS group showed higher regional microglia counts vs. controls. In vitro, at baseline, microglia secreted more IL-1beta in the in vivo LPS group than in Controls. LPS re-exposure further increased IL-1beta versus baseline. The relative IL-1beta increase was ∼4.6-fold in both cases. Discussion: Inflammatory microglial phenotype acquired during in vivo exposure to LPS is sustained and potentiated in vitro upon re-exposure to LPS. This model allows studying mechanisms of fetal neuroinflammation in utero and in vitro to identify potential therapeutic targets for early postnatal intervention. http://dx.doi.org/10.1016/j.ijdevneu.2015.04.282 ISDN2014 0341 Neuropsychological profile of children aged 5–7 years with Traumatic Brain Injury ˜ 1,∗ , Yulia Maria Jimena Sarmiento Bolanos Solovieva 2 , Luis Quintanar-Rojas 2 1 2
Universidades Federal de Paraná, Brazil Universidad Autonoma de Puebla, Mexico
Traumatic brain injury (TBI) is the leading cause of death among children and adolescents. The trauma in general is a real public health problem in any country in the world, with an upward trend