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Amelia J. Eisch - One of the best experts on this subject based on the ideXlab platform.
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time course of morphine s effects on adult hippocampal Subgranular Zone reveals preferential inhibition of cells in s phase of the cell cycle and a subpopulation of immature neurons
Neuroscience, 2008Co-Authors: Amy A. Arguello, Chitra D. Mandyam, Gwyndolen Harburg, Joshua R Schonborn, Masahiro Yamaguchi, Amelia J. EischAbstract:Abstract Opiates, such as morphine, decrease neurogenesis in the adult hippocampal Subgranular Zone (SGZ), raising the possibility that decreased neurogenesis contributes to opiate-induced cognitive deficits. However, there is an incomplete understanding of how alterations in cell cycle progression and progenitor maturation contribute to this decrease. The present study examined how morphine regulates progenitor cell cycle, cell death and immature SGZ neurons (experiment 1) as well as the progression of SGZ progenitors through key stages of maturation (experiment 2). In experiment 1, mice received sham or morphine pellets (s.c., 0 and 48 h) and bromodeoxyuridine (BrdU) 2 h prior to sacrifice (24, 72 or 96 h). Morphine decreased both the number of S phase and total cycling cells, as there were fewer cells immunoreactive (IR) for the S phase marker BrdU and the cell cycle marker Ki67. The percentage of Ki67-IR cells that were BrdU-IR was decreased after 24 but not 96 h of morphine, suggesting a disproportionate effect on S phase cells relative to all cycling cells at this time point. Cell death (activated caspase-3 counts) was increased after 24 but not 96 h. In experiment 2, nestin-green fluorescent protein (GFP) mice given BrdU 1 day prior to morphine or sham surgery (0 and 48 h, sacrifice 96 h) had fewer Ki67-IR cells, but no change in BrdU-IR cell number, suggesting that this population of BrdU-IR cells was less sensitive to morphine. Interestingly, examination of key stages of progenitor cell maturation revealed that morphine increased the percent of BrdU-IR cells that were type 2b and decreased the percent that were immature neurons. These data suggest that chronic morphine decreases SGZ neurogenesis by inhibiting dividing cells, particularly those in S phase, and progenitor cell progression to a more mature neuronal stage.
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Morphine blood levels, dependence, and regulation of hippocampal Subgranular Zone proliferation rely on administration paradigm
Neuroscience, 2008Co-Authors: Stephanie J. Fischer, Amy A. Arguello, J. J. Charlton, D. C. Fuller, Venetia Zachariou, Amelia J. EischAbstract:Chronic morphine, administered via s.c. pellet, decreases the number of proliferating cells in the dentate gyrus Subgranular Zone (SGZ) in both rats and mice. This robust morphine-induced decrease could be used to better understand mechanisms regulating adult hippocampal neurogenesis, as well as to explore the relationship between neurogenesis and drug dependence, withdrawal, and relapse behaviors. Such research would benefit enormously from identifying a route of morphine administration that produces addiction-relevant blood levels of morphine, results in a high degree of dependence, translates to both rat and mouse, and is free of the behavioral confounds of s.c. pellets. Therefore, we examined a classic chronic morphine pellet paradigm (two s.c. pellets over 5 days) versus three chronic morphine injection paradigms (escalating dose i.p. injections over 2, 5, or 10 days) for their effect in adult male C57BL/6J mice. We assessed blood morphine levels, SGZ proliferation, and drug dependence as assessed by tolerance to locomotion sensitization and naloxone-precipitated withdrawal. The pellet paradigm produced high and relatively stable blood levels of morphine, a high degree of dependence, and a significant decrease in SGZ proliferation. In contrast, the three injection paradigms produced transient spikes in morphine blood levels, significantly less dependence than the pellet paradigm, and no significant decrease in SGZ proliferation. These data show that regulation of mouse SGZ proliferation requires high and relatively stable blood levels of morphine, and provide critical knowledge for the design of future studies to probe the relationship between addiction and neurogenesis.
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Determination of key aspects of precursor cell proliferation, cell cycle length and kinetics in the adult mouse Subgranular Zone.
Neuroscience, 2007Co-Authors: Chitra D. Mandyam, Gwyndolen Harburg, Amelia J. EischAbstract:Abstract Neurogenesis studies on the adult mouse hippocampal Subgranular Zone (SGZ) typically report increases or decreases in proliferation. However, key information is lacking about these proliferating SGZ precursors, from the fundamental—what dose of bromodeoxyuridine (BrdU) is appropriate for labeling all S phase cells?—to the detailed—what are the kinetics of BrdU-labeled cells and their progeny? To address these questions, adult C57BL/6J mice were injected with BrdU and BrdU-immunoreactive (IR) cells were quantified. Initial experiments with a range of BrdU doses (25–500 mg/kg) suggested that 150 mg/kg labels all actively dividing precursors in the mouse SGZ. Experiments using a saturating dose of BrdU suggested BrdU bioavailability is less than 15 min, notably shorter than in the developing mouse brain. We next explored precursor division and maturation by tracking the number of BrdU-IR cells and colabeling of BrdU with other cell cycle proteins from 15 min to 30 days after BrdU. We found that BrdU and the Gap2 and mitosis (G 2 /M) phase protein pHisH3 maximally colocalized 8 h after BrdU, indicating that the mouse SGZ precursor cell cycle length is 14 h. In addition, triple labeling with BrdU and proliferating cell nuclear antigen (PCNA) and Ki-67 showed that BrdU-IR precursors and/or their progeny express these endogenous cell cycle proteins up to 4 days after BrdU injection. However, the proportion of BrdU/Ki-67-IR cells declined at a greater rate than the proportion of BrdU/PCNA-IR cells. This suggests that PCNA protein is detectable long after cell cycle exit, and that reliance on PCNA may overestimate the length of time a cell remains in the cell cycle. These findings will be critical for future studies examining the regulation of SGZ precursor kinetics in adult mice, and hopefully will encourage the field to move beyond counting BrdU-IR cells to a more mechanistic analysis of adult neurogenesis.
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Chronic morphine induces premature mitosis of proliferating cells in the adult mouse Subgranular Zone
Journal of Neuroscience Research, 2004Co-Authors: Chitra D. Mandyam, Rebekah D. Norris, Amelia J. EischAbstract:The birth of cells with neurogenic potential in the adult brain is assessed commonly by detection of exogenous S phase markers, such as bromodeoxyuridine (BrdU). Analysis of other phases of the cell cycle, however, can provide insight into how external factors, such as opiates, influence the cycling of newly born cells. To this end, we examined the expression of two endogenous cell cycle markers in relation to BrdU: proliferating cell nuclear antigen (PCNA) and phosphorylated histone H3 (pHisH3). Two hours after one intraperitoneal BrdU injection, BrdU-, PCNA-, and pHisH3-immunoreactive (IR) cells exhibited similar distribution in the adult mouse Subgranular Zone (SGZ). Quantitative analysis within the SGZ revealed a relative abundance of cells labeled for PCNA > BrdU >> pHisH3. Similar to our reports in rat SGZ, chronic morphine treatment decreased BrdU- and PCNA-IR cells in mouse SGZ by 28 and 38%, respectively. We also show that pHisH3-IR cells are influenced by chronic morphine to a greater extent (58% decrease) than are BrdU- or PCNA-IR cells. Cell cycle phase analysis of SGZ BrdU-IR cells using triple labeling for BrdU, PCNA, and pHisH3 revealed premature mitosis in chronic morphine-treated mice. These results suggest that morphine-treated mice have a shorter Gap2/mitosis (G2/M) phase when compared to sham-treated mice. These findings demonstrate the power of using a combination of exogenous and endogenous cell cycle markers and nuclear morphology to track proliferating cells through different phases of the cell cycle and to reveal the regulation of cell cycle phase by chronic morphine. © 2004 Wiley-Liss, Inc.
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chronic morphine induces premature mitosis of proliferating cells in the adult mouse Subgranular Zone
Journal of Neuroscience Research, 2004Co-Authors: Chitra D. Mandyam, Rebekah D. Norris, Amelia J. EischAbstract:The birth of cells with neurogenic potential in the adult brain is assessed commonly by detection of exogenous S phase markers, such as bromodeoxyuridine (BrdU). Analysis of other phases of the cell cycle, however, can provide insight into how external factors, such as opiates, influence the cycling of newly born cells. To this end, we examined the expression of two endogenous cell cycle markers in relation to BrdU: proliferating cell nuclear antigen (PCNA) and phosphorylated histone H3 (pHisH3). Two hours after one intraperitoneal BrdU injection, BrdU-, PCNA-, and pHisH3-immunoreactive (IR) cells exhibited similar distribution in the adult mouse Subgranular Zone (SGZ). Quantitative analysis within the SGZ revealed a relative abundance of cells labeled for PCNA > BrdU >> pHisH3. Similar to our reports in rat SGZ, chronic morphine treatment decreased BrdU- and PCNA-IR cells in mouse SGZ by 28 and 38%, respectively. We also show that pHisH3-IR cells are influenced by chronic morphine to a greater extent (58% decrease) than are BrdU- or PCNA-IR cells. Cell cycle phase analysis of SGZ BrdU-IR cells using triple labeling for BrdU, PCNA, and pHisH3 revealed premature mitosis in chronic morphine-treated mice. These results suggest that morphine-treated mice have a shorter Gap2/mitosis (G(2)/M) phase when compared to sham-treated mice. These findings demonstrate the power of using a combination of exogenous and endogenous cell cycle markers and nuclear morphology to track proliferating cells through different phases of the cell cycle and to reveal the regulation of cell cycle phase by chronic morphine.
In Koo Hwang - One of the best experts on this subject based on the ideXlab platform.
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long term administration of scopolamine interferes with nerve cell proliferation differentiation and migration in adult mouse hippocampal dentate gyrus but it does not induce cell death
Neural Regeneration Research, 2014Co-Authors: Bingchun Yan, In Koo Hwang, Bai Hui Chen, Joon Ha Park, Jeong Hwi Cho, In Hye Kim, Ji Hyeon Ahn, Jae-chul Lee, Jun Hwi Cho, Yun Lyul LeeAbstract:Long-term administration of scopolamine, a muscarinic receptor antagonist, can inhibit the survival of newly generated cells, but its effect on the proliferation, differentiation and migration of nerve cells in the adult mouse hippocampal dentate gyrus remain poorly understood. In this study, we used immunohistochemistry and western blot methods to weekly detect the biological behaviors of nerve cells in the hippocampal dentate gyrus of adult mice that received intraperitoneal administration of scopolamine for 4 weeks. Expression of neuronal nuclear antigen (NeuN; a neuronal marker) and Fluoro-Jade B (a marker for the localization of neuronal degeneration) was also detected. After scopolamine treatment, mouse hippocampal neurons did not die, and Ki-67 (a marker for proliferating cells)-immunoreactive cells were reduced in number and reached the lowest level at 4 weeks. Doublecortin (DCX; a marker for newly generated neurons)-immunoreactive cells were gradually shortened in length and reduced in number with time. After scopolamine treatment for 4 weeks, nearly all of the 5-bromo-2′-deoxyuridine (BrdU)-labeled newly generated cells were located in the Subgranular Zone of the dentate gyrus, but they did not migrate into the granule cell layer. Few mature BrdU/NeuN double-labeled cells were seen in the Subgranular Zone of the dentate gyrus. These findings suggest that long-term administration of scopolamine interferes with the proliferation, differentiation and migration of nerve cells in the adult mouse hippocampal dentate gyrus, but it does not induce cell death.
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Effects of treadmill exercise on neural stem cells, cell proliferation, and neuroblast differentiation in the Subgranular Zone of the dentate gyrus in cyclooxygenase-2 knockout mice.
Neurochemical Research, 2013Co-Authors: Sung Min Nam, Mooho Won, Je Kyung Seong, In Koo Hwang, Dae Young Yoo, Hyo Young Jung, Jung Hoon Choi, Jong Whi Kim, Woosuk Kim, Yeo Sung YoonAbstract:Cyclooxygenase-2 (COX-2) function has been implicated in a number of physiological processes, including inflammatory responses, synaptic transmission, and synaptic plasticity in the brain. However, the specific role of COX-2 in exercise-induced neurogenesis is still debatable. Here, we assessed the role of COX-2 in exercise-induced plasticity by comparing COX-2 knockout mice to wild-type control littermates. We investigated the number of neural stem cells, and the degree of cell proliferation and neuronal differentiation in COX-2 knockout and its wild-type mice that either exercised or remained inactive. Wild-type and COX-2 knockout mice were put on a treadmill and were either sedentary or were forced to run 1 h/day for five consecutive days at a pace of 10–12 m/min for 5 weeks. Loss of COX-2 expression in the knockout mice was confirmed with two measures: (1) COX immunolabeling in the hippocampus, and (2) the identification of abnormal kidney development using hematoxylin and eosin staining, including subcapsular glomerular hypoplasia and hypertrophy of the deeper cortical glomeruli. Compared to wild-type mice, COX-2 knockout mice exhibited a significant reduction in the neural stem cells (nestin-positive cells), cell proliferation (Ki67-positive cells), and neuroblast differentiation (doublecortin-positive cells). In contrast, exercise significantly increased the neural stem cells, cell proliferation, and neuroblast differentiation in both the wild-type and COX-2 knockout mice although the NeuN-immunoreactive neurons were similar in all groups. Expression of phosphorylated cAMP-response element binding protein was decreased in knockout mice. Exercise increased its expression in the Subgranular Zone of the dentate gyrus in both wild-type and knockout mice. These results suggest that the COX-2 pathway is one of important factors on neural stem cells, cell proliferation and neuroblast differentiation in sedentary mice. The ability of exercise to increase these types of neural plasticity, regardless of COX-2 signaling, suggests that the effects of exercise on neural stem cells, cell proliferation, and neuroblast differentiation are induced via a pathway that is independent of COX-2.
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Zizyphus enhances cell proliferation and neuroblast differentiation in the Subgranular Zone of the dentate gyrus in middle-aged mice.
Journal of Medicinal Food, 2011Co-Authors: In Koo Hwang, Kiyeon Yoo, Dae Young Yoo, Jung Hoon Choi, Choong Hyun Lee, Il-jun Kang, Dae Young Kwon, Young Sup Kim, Dong-woo Kim, Mooho WonAbstract:Abstract Zizyphus jujuba is considered to have various physiological functions in the brain. We obtained a Z. jujuba methanol extract (ZJE) and observed its effects on neurogenesis in middle-aged mice. Twelve-month-old mice received repeated oral administrations of ZJE for 30 days. The administration of ZJE significantly increased the number of Ki67 (a marker for cell proliferation)-positive cells in the Subgranular Zone of the dentate gyrus of middle-aged mice. Furthermore, ZJE significantly increased doublecortin (a marker for neuroblast differentiation)-immunoreactive neuroblasts with tertiary dendrites, but not those without tertiary dendrites, in the dentate gyrus. In addition, doublecortin protein levels in the ZJE-treated groups tended to increase dose-dependently. These results suggest that the repeated supplement of ZJE may increase the hippocampal plasticity in middle-aged mice.
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effects of electroacupuncture at zusanli and baihui on brain derived neurotrophic factor and cyclic amp response element binding protein in the hippocampal dentate gyrus
Journal of Veterinary Medical Science, 2010Co-Authors: In Koo Hwang, Sun Shin Yi, Hwa Young Youn, Je Kyung Seong, Jin Young Chung, Yeo Sung YoonAbstract:Previously, we observed that electroacupuncture (EA) at ST36 (Zusanli) and GV20 (Baihui) enhanced cell proliferation and neuroblast differentiation in the rat dentate gyrus. In this study, we investigated the possible mechanisms of EA in this effect. For this, we applied EA at ST36 and GV20 of Wistar rats (13-week-old) once a day for 3 weeks. Application of EA at these acupoints significantly increased the number of phosphorylated cyclic AMP response element-binding protein (pCREB)-immunoreactive cells in the dentate gyrus. In addition, EA significantly increased the levels of brain-derived neurotrophic factor (BDNF) and pCREB protein in the dentate gyrus. The administration of K252a, an inhibitor of BDNF receptor, significantly reduced cell proliferation in the Subgranular Zone of dentate gyrus. These results suggest that EA significantly increased neuroblast plasticity via pCREB and BDNF activation in the dentate gyrus.
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comparing the effects of acupuncture and electroacupuncture at zusanli and baihui on cell proliferation and neuroblast differentiation in the rat hippocampus
Journal of Veterinary Medical Science, 2010Co-Authors: In Koo Hwang, Sun Shin Yi, Hwa Young Youn, Je Kyung Seong, Jin Young Chung, Yeo Sung YoonAbstract:We compared the effects of acupuncture and electroacupuncture on cell proliferation and neuroblast differentiation using specific markers, Ki67 and doublecortin (DCX), in the Subgranular Zone of the dentate gyrus (SZDG) in 13-week old Wistar rats. Acupuncture and electroacupuncture were applied simultaneously in the acu-points, ST36 (Zusanli) and GV20 (Baihui), once a day for 3 weeks. Acupuncture and electroacupuncture at these acu-points significantly increased the number of Ki67-positive cells and DCX-immunoreactive neuroblasts compared to the control or sham acupuncture group. Electroacupuncture treatment significantly increased the number of well-developed (tertiary) dendrites in the SZDG compared to acupuncture treatment. These results suggest that both acupuncture and electroacupuncture increase neurogenesis in the normal, but that electroacupuncture has greater effects on neuroblast plasticity than acupuncture in the dentate gyrus.
Chitra D. Mandyam - One of the best experts on this subject based on the ideXlab platform.
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time course of morphine s effects on adult hippocampal Subgranular Zone reveals preferential inhibition of cells in s phase of the cell cycle and a subpopulation of immature neurons
Neuroscience, 2008Co-Authors: Amy A. Arguello, Chitra D. Mandyam, Gwyndolen Harburg, Joshua R Schonborn, Masahiro Yamaguchi, Amelia J. EischAbstract:Abstract Opiates, such as morphine, decrease neurogenesis in the adult hippocampal Subgranular Zone (SGZ), raising the possibility that decreased neurogenesis contributes to opiate-induced cognitive deficits. However, there is an incomplete understanding of how alterations in cell cycle progression and progenitor maturation contribute to this decrease. The present study examined how morphine regulates progenitor cell cycle, cell death and immature SGZ neurons (experiment 1) as well as the progression of SGZ progenitors through key stages of maturation (experiment 2). In experiment 1, mice received sham or morphine pellets (s.c., 0 and 48 h) and bromodeoxyuridine (BrdU) 2 h prior to sacrifice (24, 72 or 96 h). Morphine decreased both the number of S phase and total cycling cells, as there were fewer cells immunoreactive (IR) for the S phase marker BrdU and the cell cycle marker Ki67. The percentage of Ki67-IR cells that were BrdU-IR was decreased after 24 but not 96 h of morphine, suggesting a disproportionate effect on S phase cells relative to all cycling cells at this time point. Cell death (activated caspase-3 counts) was increased after 24 but not 96 h. In experiment 2, nestin-green fluorescent protein (GFP) mice given BrdU 1 day prior to morphine or sham surgery (0 and 48 h, sacrifice 96 h) had fewer Ki67-IR cells, but no change in BrdU-IR cell number, suggesting that this population of BrdU-IR cells was less sensitive to morphine. Interestingly, examination of key stages of progenitor cell maturation revealed that morphine increased the percent of BrdU-IR cells that were type 2b and decreased the percent that were immature neurons. These data suggest that chronic morphine decreases SGZ neurogenesis by inhibiting dividing cells, particularly those in S phase, and progenitor cell progression to a more mature neuronal stage.
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Determination of key aspects of precursor cell proliferation, cell cycle length and kinetics in the adult mouse Subgranular Zone.
Neuroscience, 2007Co-Authors: Chitra D. Mandyam, Gwyndolen Harburg, Amelia J. EischAbstract:Abstract Neurogenesis studies on the adult mouse hippocampal Subgranular Zone (SGZ) typically report increases or decreases in proliferation. However, key information is lacking about these proliferating SGZ precursors, from the fundamental—what dose of bromodeoxyuridine (BrdU) is appropriate for labeling all S phase cells?—to the detailed—what are the kinetics of BrdU-labeled cells and their progeny? To address these questions, adult C57BL/6J mice were injected with BrdU and BrdU-immunoreactive (IR) cells were quantified. Initial experiments with a range of BrdU doses (25–500 mg/kg) suggested that 150 mg/kg labels all actively dividing precursors in the mouse SGZ. Experiments using a saturating dose of BrdU suggested BrdU bioavailability is less than 15 min, notably shorter than in the developing mouse brain. We next explored precursor division and maturation by tracking the number of BrdU-IR cells and colabeling of BrdU with other cell cycle proteins from 15 min to 30 days after BrdU. We found that BrdU and the Gap2 and mitosis (G 2 /M) phase protein pHisH3 maximally colocalized 8 h after BrdU, indicating that the mouse SGZ precursor cell cycle length is 14 h. In addition, triple labeling with BrdU and proliferating cell nuclear antigen (PCNA) and Ki-67 showed that BrdU-IR precursors and/or their progeny express these endogenous cell cycle proteins up to 4 days after BrdU injection. However, the proportion of BrdU/Ki-67-IR cells declined at a greater rate than the proportion of BrdU/PCNA-IR cells. This suggests that PCNA protein is detectable long after cell cycle exit, and that reliance on PCNA may overestimate the length of time a cell remains in the cell cycle. These findings will be critical for future studies examining the regulation of SGZ precursor kinetics in adult mice, and hopefully will encourage the field to move beyond counting BrdU-IR cells to a more mechanistic analysis of adult neurogenesis.
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Chronic morphine induces premature mitosis of proliferating cells in the adult mouse Subgranular Zone
Journal of Neuroscience Research, 2004Co-Authors: Chitra D. Mandyam, Rebekah D. Norris, Amelia J. EischAbstract:The birth of cells with neurogenic potential in the adult brain is assessed commonly by detection of exogenous S phase markers, such as bromodeoxyuridine (BrdU). Analysis of other phases of the cell cycle, however, can provide insight into how external factors, such as opiates, influence the cycling of newly born cells. To this end, we examined the expression of two endogenous cell cycle markers in relation to BrdU: proliferating cell nuclear antigen (PCNA) and phosphorylated histone H3 (pHisH3). Two hours after one intraperitoneal BrdU injection, BrdU-, PCNA-, and pHisH3-immunoreactive (IR) cells exhibited similar distribution in the adult mouse Subgranular Zone (SGZ). Quantitative analysis within the SGZ revealed a relative abundance of cells labeled for PCNA > BrdU >> pHisH3. Similar to our reports in rat SGZ, chronic morphine treatment decreased BrdU- and PCNA-IR cells in mouse SGZ by 28 and 38%, respectively. We also show that pHisH3-IR cells are influenced by chronic morphine to a greater extent (58% decrease) than are BrdU- or PCNA-IR cells. Cell cycle phase analysis of SGZ BrdU-IR cells using triple labeling for BrdU, PCNA, and pHisH3 revealed premature mitosis in chronic morphine-treated mice. These results suggest that morphine-treated mice have a shorter Gap2/mitosis (G2/M) phase when compared to sham-treated mice. These findings demonstrate the power of using a combination of exogenous and endogenous cell cycle markers and nuclear morphology to track proliferating cells through different phases of the cell cycle and to reveal the regulation of cell cycle phase by chronic morphine. © 2004 Wiley-Liss, Inc.
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chronic morphine induces premature mitosis of proliferating cells in the adult mouse Subgranular Zone
Journal of Neuroscience Research, 2004Co-Authors: Chitra D. Mandyam, Rebekah D. Norris, Amelia J. EischAbstract:The birth of cells with neurogenic potential in the adult brain is assessed commonly by detection of exogenous S phase markers, such as bromodeoxyuridine (BrdU). Analysis of other phases of the cell cycle, however, can provide insight into how external factors, such as opiates, influence the cycling of newly born cells. To this end, we examined the expression of two endogenous cell cycle markers in relation to BrdU: proliferating cell nuclear antigen (PCNA) and phosphorylated histone H3 (pHisH3). Two hours after one intraperitoneal BrdU injection, BrdU-, PCNA-, and pHisH3-immunoreactive (IR) cells exhibited similar distribution in the adult mouse Subgranular Zone (SGZ). Quantitative analysis within the SGZ revealed a relative abundance of cells labeled for PCNA > BrdU >> pHisH3. Similar to our reports in rat SGZ, chronic morphine treatment decreased BrdU- and PCNA-IR cells in mouse SGZ by 28 and 38%, respectively. We also show that pHisH3-IR cells are influenced by chronic morphine to a greater extent (58% decrease) than are BrdU- or PCNA-IR cells. Cell cycle phase analysis of SGZ BrdU-IR cells using triple labeling for BrdU, PCNA, and pHisH3 revealed premature mitosis in chronic morphine-treated mice. These results suggest that morphine-treated mice have a shorter Gap2/mitosis (G(2)/M) phase when compared to sham-treated mice. These findings demonstrate the power of using a combination of exogenous and endogenous cell cycle markers and nuclear morphology to track proliferating cells through different phases of the cell cycle and to reveal the regulation of cell cycle phase by chronic morphine.
Mooho Won - One of the best experts on this subject based on the ideXlab platform.
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Effects of treadmill exercise on neural stem cells, cell proliferation, and neuroblast differentiation in the Subgranular Zone of the dentate gyrus in cyclooxygenase-2 knockout mice.
Neurochemical Research, 2013Co-Authors: Sung Min Nam, Mooho Won, Je Kyung Seong, In Koo Hwang, Dae Young Yoo, Hyo Young Jung, Jung Hoon Choi, Jong Whi Kim, Woosuk Kim, Yeo Sung YoonAbstract:Cyclooxygenase-2 (COX-2) function has been implicated in a number of physiological processes, including inflammatory responses, synaptic transmission, and synaptic plasticity in the brain. However, the specific role of COX-2 in exercise-induced neurogenesis is still debatable. Here, we assessed the role of COX-2 in exercise-induced plasticity by comparing COX-2 knockout mice to wild-type control littermates. We investigated the number of neural stem cells, and the degree of cell proliferation and neuronal differentiation in COX-2 knockout and its wild-type mice that either exercised or remained inactive. Wild-type and COX-2 knockout mice were put on a treadmill and were either sedentary or were forced to run 1 h/day for five consecutive days at a pace of 10–12 m/min for 5 weeks. Loss of COX-2 expression in the knockout mice was confirmed with two measures: (1) COX immunolabeling in the hippocampus, and (2) the identification of abnormal kidney development using hematoxylin and eosin staining, including subcapsular glomerular hypoplasia and hypertrophy of the deeper cortical glomeruli. Compared to wild-type mice, COX-2 knockout mice exhibited a significant reduction in the neural stem cells (nestin-positive cells), cell proliferation (Ki67-positive cells), and neuroblast differentiation (doublecortin-positive cells). In contrast, exercise significantly increased the neural stem cells, cell proliferation, and neuroblast differentiation in both the wild-type and COX-2 knockout mice although the NeuN-immunoreactive neurons were similar in all groups. Expression of phosphorylated cAMP-response element binding protein was decreased in knockout mice. Exercise increased its expression in the Subgranular Zone of the dentate gyrus in both wild-type and knockout mice. These results suggest that the COX-2 pathway is one of important factors on neural stem cells, cell proliferation and neuroblast differentiation in sedentary mice. The ability of exercise to increase these types of neural plasticity, regardless of COX-2 signaling, suggests that the effects of exercise on neural stem cells, cell proliferation, and neuroblast differentiation are induced via a pathway that is independent of COX-2.
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Zizyphus enhances cell proliferation and neuroblast differentiation in the Subgranular Zone of the dentate gyrus in middle-aged mice.
Journal of Medicinal Food, 2011Co-Authors: In Koo Hwang, Kiyeon Yoo, Dae Young Yoo, Jung Hoon Choi, Choong Hyun Lee, Il-jun Kang, Dae Young Kwon, Young Sup Kim, Dong-woo Kim, Mooho WonAbstract:Abstract Zizyphus jujuba is considered to have various physiological functions in the brain. We obtained a Z. jujuba methanol extract (ZJE) and observed its effects on neurogenesis in middle-aged mice. Twelve-month-old mice received repeated oral administrations of ZJE for 30 days. The administration of ZJE significantly increased the number of Ki67 (a marker for cell proliferation)-positive cells in the Subgranular Zone of the dentate gyrus of middle-aged mice. Furthermore, ZJE significantly increased doublecortin (a marker for neuroblast differentiation)-immunoreactive neuroblasts with tertiary dendrites, but not those without tertiary dendrites, in the dentate gyrus. In addition, doublecortin protein levels in the ZJE-treated groups tended to increase dose-dependently. These results suggest that the repeated supplement of ZJE may increase the hippocampal plasticity in middle-aged mice.
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cyclosporine a reduces dendritic outgrowth of neuroblasts in the Subgranular Zone of the dentate gyrus in c57bl 6 mice
Neurochemical Research, 2010Co-Authors: In Koo Hwang, Kiyeon Yoo, Je Kyung Seong, Yeo Sung Yoon, Jung Hoon Choi, Choong Hyun Lee, Jae Hoon Shin, Jeong Ho Park, Mooho WonAbstract:In the present study, we observed the effects of cyclosporine A (CsA), an efficient immunosuppressant, on cell proliferation and neuroblast differentiation in the Subgranular Zone of the dentate gyrus (SZDG) in normal C57BL/6 mice using Ki67 and doublecortin (DCX) immunohistochemical staining, respectively. At 8 weeks of age, vehicle (physiological saline) or CsA was daily administered (40 mg/kg, i.p.) for 1 week. Animals were sacrificed at 2 weeks after last administration. CsA treatment did not show any influences in neurons, astrocytes and microglia based on immunohistochemistry for its markers, respectively. However, in the CsA-treated group, Fluoro-Jade B, a marker for neurodegeneration, positive cells were found in the SZDG, not in the vehicle-treated group. In the vehicle-treated group, Ki67 immunoreactive (+) nuclei were clustered in the SZDG, whereas in the CsA-treated group Ki67+ nuclei were scattered in the SZDG, showing no difference in cell numbers. Numbers of DCX+ neuroblasts with well-developed processes (tertiary dendrites) were much lower in the CsA-treated group than those in the vehicle-treated group; however, numbers of DCX+ neuroblasts with secondary dendrites were similar in both the groups. These results suggest that CsA significantly reduces dendritic outgrowth and complexity from neuroblasts in the SZDG without any affecting in neurons, astrocytes and microglia in normal mice.
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(-)-Epigallocatechin-3-gallate increases cell proliferation and neuroblasts in the Subgranular Zone of the dentate gyrus in adult mice.
Phytotherapy Research, 2009Co-Authors: Kiyeon Yoo, In Koo Hwang, Jung Hoon Choi, Choong Hyun Lee, Soon Ok Lee, Sag-myung Han, Hyung-cheul Shin, Il-jun Kang, Mooho WonAbstract:Neurogenesis is regulated by several factors such as age, stress and pharmacological agents. We observed the effects of (-)-epigallocatechin-3-gallate (EGCG), a major catechin of green tea, on neurogenesis in mice. The animals were orally administered EGCG for 4 weeks. Brain sections were stained using a marker for cell proliferation (Ki67 and BrdU) and neuroblasts (doublecortin, DCX). In all groups, Ki67, BrdU and DCX immunoreaction were observed in the Subgranular Zone of the dentate gyrus. Oral administration of EGCG significantly increased the number of Ki67-, BrdU- and DCX-immunoreactive cells as well as BrdU/DCX-colabled cells in the Subgranular Zone when compared to those in the vehicle-treated group. These results indicate that oral administration of EGCG can enhance cell proliferation and increase the number of neuroblasts in mice hippocampal dentate gyrus.
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age related differentiation in newly generated dcx immunoreactive neurons in the Subgranular Zone of the gerbil dentate gyrus
Neurochemical Research, 2008Co-Authors: In Koo Hwang, Kiyeon Yoo, Youngkeun Ahn, In Se Lee, Youngguen Kwon, Sun Shin Yi, Je Kyung Seong, Yeo Sung Yoon, Mooho WonAbstract:In the present study, we investigated age-related changes of newborn neurons in the gerbil dentate gyrus using doublecortin (DCX), a marker of neuronal progenitors which differentiate into neurons in the brain. In the postnatal month 1 (PM 1) group, DCX immunoreactivity was detected in the Subgranular Zone of the dentate gyrus, but DCX immunoreactive neurons did not have fully developed processes. Thereafter, DCX immunoreactivity and its protein levels in the dentate gyrus were found to decrease with age. Between PM 3 and PM 18, DCX immunoreactive neuronal progenitors showed well-developed processes which projected to the granular layer of the dentate gyrus, but at PM 24, a few DCX immunoreactive neuronal progenitors were detected in the Subgranular Zone of the dentate gyrus. DCX protein level in the dentate gyrus at PM 1 was high, thereafter levels of DCX were decreased with time. The authors suggest that a decrease of DCX immunoreactivity and its protein level with age may be associated with aging processes in the hippocampal dentate gyrus.
Kiyeon Yoo - One of the best experts on this subject based on the ideXlab platform.
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Zizyphus enhances cell proliferation and neuroblast differentiation in the Subgranular Zone of the dentate gyrus in middle-aged mice.
Journal of Medicinal Food, 2011Co-Authors: In Koo Hwang, Kiyeon Yoo, Dae Young Yoo, Jung Hoon Choi, Choong Hyun Lee, Il-jun Kang, Dae Young Kwon, Young Sup Kim, Dong-woo Kim, Mooho WonAbstract:Abstract Zizyphus jujuba is considered to have various physiological functions in the brain. We obtained a Z. jujuba methanol extract (ZJE) and observed its effects on neurogenesis in middle-aged mice. Twelve-month-old mice received repeated oral administrations of ZJE for 30 days. The administration of ZJE significantly increased the number of Ki67 (a marker for cell proliferation)-positive cells in the Subgranular Zone of the dentate gyrus of middle-aged mice. Furthermore, ZJE significantly increased doublecortin (a marker for neuroblast differentiation)-immunoreactive neuroblasts with tertiary dendrites, but not those without tertiary dendrites, in the dentate gyrus. In addition, doublecortin protein levels in the ZJE-treated groups tended to increase dose-dependently. These results suggest that the repeated supplement of ZJE may increase the hippocampal plasticity in middle-aged mice.
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cyclosporine a reduces dendritic outgrowth of neuroblasts in the Subgranular Zone of the dentate gyrus in c57bl 6 mice
Neurochemical Research, 2010Co-Authors: In Koo Hwang, Kiyeon Yoo, Je Kyung Seong, Yeo Sung Yoon, Jung Hoon Choi, Choong Hyun Lee, Jae Hoon Shin, Jeong Ho Park, Mooho WonAbstract:In the present study, we observed the effects of cyclosporine A (CsA), an efficient immunosuppressant, on cell proliferation and neuroblast differentiation in the Subgranular Zone of the dentate gyrus (SZDG) in normal C57BL/6 mice using Ki67 and doublecortin (DCX) immunohistochemical staining, respectively. At 8 weeks of age, vehicle (physiological saline) or CsA was daily administered (40 mg/kg, i.p.) for 1 week. Animals were sacrificed at 2 weeks after last administration. CsA treatment did not show any influences in neurons, astrocytes and microglia based on immunohistochemistry for its markers, respectively. However, in the CsA-treated group, Fluoro-Jade B, a marker for neurodegeneration, positive cells were found in the SZDG, not in the vehicle-treated group. In the vehicle-treated group, Ki67 immunoreactive (+) nuclei were clustered in the SZDG, whereas in the CsA-treated group Ki67+ nuclei were scattered in the SZDG, showing no difference in cell numbers. Numbers of DCX+ neuroblasts with well-developed processes (tertiary dendrites) were much lower in the CsA-treated group than those in the vehicle-treated group; however, numbers of DCX+ neuroblasts with secondary dendrites were similar in both the groups. These results suggest that CsA significantly reduces dendritic outgrowth and complexity from neuroblasts in the SZDG without any affecting in neurons, astrocytes and microglia in normal mice.
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(-)-Epigallocatechin-3-gallate increases cell proliferation and neuroblasts in the Subgranular Zone of the dentate gyrus in adult mice.
Phytotherapy Research, 2009Co-Authors: Kiyeon Yoo, In Koo Hwang, Jung Hoon Choi, Choong Hyun Lee, Soon Ok Lee, Sag-myung Han, Hyung-cheul Shin, Il-jun Kang, Mooho WonAbstract:Neurogenesis is regulated by several factors such as age, stress and pharmacological agents. We observed the effects of (-)-epigallocatechin-3-gallate (EGCG), a major catechin of green tea, on neurogenesis in mice. The animals were orally administered EGCG for 4 weeks. Brain sections were stained using a marker for cell proliferation (Ki67 and BrdU) and neuroblasts (doublecortin, DCX). In all groups, Ki67, BrdU and DCX immunoreaction were observed in the Subgranular Zone of the dentate gyrus. Oral administration of EGCG significantly increased the number of Ki67-, BrdU- and DCX-immunoreactive cells as well as BrdU/DCX-colabled cells in the Subgranular Zone when compared to those in the vehicle-treated group. These results indicate that oral administration of EGCG can enhance cell proliferation and increase the number of neuroblasts in mice hippocampal dentate gyrus.
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Effects of Treadmill Exercise on Cell Proliferation and Differentiation in the Subgranular Zone of the Dentate Gyrus in a Rat Model of Type II Diabetes
Neurochemical Research, 2008Co-Authors: In Koo Hwang, Kiyeon Yoo, Yo Na Kim, Il Yong Kim, Ok Kyu Park, Bingchun Yan, Tongkun Pai, Wook SongAbstract:In the present study, we investigated the effects of a treadmill exercise on serum glucose levels and Ki67 and doublecortin (DCX) immunoreactivity, which is a marker of cell proliferation expressed during cell cycles except G0 and early G1 and a marker of progenitors differentiating into neurons, respectively, in the Subgranular Zone of the dentate gyrus (SZDG) using a type II diabetic model. At 6 weeks of age, Zucker lean control (ZLC) and Zucker diabetic fatty (ZDF) rats were put on a treadmill with or without running for 1 h/day/5 consecutive days at 22 m/min for 5 weeks. Body weight was significantly increased in the control (without running)-ZDF rats compared to that in the other groups. In the control groups blood glucose levels were increased by 392.7 mg/dl in the control-ZDF rats and by 143.3 mg/dl in the control-ZLC rats. However, in the exercise groups, blood glucose levels were similar between the exercise-ZLC and ZDF rats: The blood glucose levels were 110.0 and 118.2 mg/dl, respectively. Ki67 positive nuclei were detected in the SZDG in control and exercise groups. The number of Ki67 positive nuclei was significantly high in exercise groups compared to that in the control groups. In addition, Ki67 positive cells were abundant in ZLC groups compared to those in ZDF groups. DCX-immunoreactive structures in the control-ZDF rats were lower than that in the control-ZLC rats. In the exercise groups, DCX-immunoreactive structures (somata and processes with tertiary dendrites) and DCX protein levels were markedly increased in both the exercise-ZLC and ZDF rats compared to that in the control groups. These results suggest that a treadmill exercise reduces blood glucose levels in ZDF rats and increases cell proliferation and differentiation in the SZDG in ZLC and ZDF rats compared to those in control groups.
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age related differentiation in newly generated dcx immunoreactive neurons in the Subgranular Zone of the gerbil dentate gyrus
Neurochemical Research, 2008Co-Authors: In Koo Hwang, Kiyeon Yoo, Youngkeun Ahn, In Se Lee, Youngguen Kwon, Sun Shin Yi, Je Kyung Seong, Yeo Sung Yoon, Mooho WonAbstract:In the present study, we investigated age-related changes of newborn neurons in the gerbil dentate gyrus using doublecortin (DCX), a marker of neuronal progenitors which differentiate into neurons in the brain. In the postnatal month 1 (PM 1) group, DCX immunoreactivity was detected in the Subgranular Zone of the dentate gyrus, but DCX immunoreactive neurons did not have fully developed processes. Thereafter, DCX immunoreactivity and its protein levels in the dentate gyrus were found to decrease with age. Between PM 3 and PM 18, DCX immunoreactive neuronal progenitors showed well-developed processes which projected to the granular layer of the dentate gyrus, but at PM 24, a few DCX immunoreactive neuronal progenitors were detected in the Subgranular Zone of the dentate gyrus. DCX protein level in the dentate gyrus at PM 1 was high, thereafter levels of DCX were decreased with time. The authors suggest that a decrease of DCX immunoreactivity and its protein level with age may be associated with aging processes in the hippocampal dentate gyrus.
