Inflammation-induced Gro1 triggers senescence in neuronal progenitors: effects of estradiol

Abstract Background Inflammation has been proposed to contribute to the decline in adult hippocampal neurogenesis. Proinflammatory cytokines activate transcription of chemokine growth-regulated oncogene α (Gro1) in human and murine hippocampal neuronal progenitor cells (NPC). The goal of this study was to investigate the effects of Gro1 on hippocampal neurogenesis in the presence of inflammation. Methods Human hippocampal NPC were transfected with lentivirus expressing Gro1, and murine NPC and hippocampal neuronal HT-22 cells were treated with Gro1 protein. A plasmid expressing mGro1 was electroporated in the hippocampus of newborn mice that were sacrificed 10 days later. Adult male and female mice were injected with lipopolysaccharide (LPS; 1 mg/kg, i.p in five daily injections) or normal saline. Adult male mice were implanted with pellets releasing 17-β estradiol (E2; 2.5 mg/pellet, 41.666 μg/day release) or placebo for 6 weeks and challenged with LPS or normal saline as above. In both experiments, mice were sacrificed 3 h after the last injection. Hippocampal markers of neurogenesis were assessed in vitro and in vivo by Western blot, real-time PCR, and immunohisto/cytochemistry. Results Gro1 induced premature senescence in NPC and HT-22 cells, activating senescence-associated β-galactosidase and the cell cycle inhibitor p16 and suppressing neuroblast proliferation and expression of doublecortin (DCX) and neuron-specific class III beta-tubulin (Tuj-1), both neuroblast markers, while promoting proliferation of neural glial antigen 2 (Ng2)-positive oligodendrocytes. Gro1 overexpression in the hippocampus of newborn mice resulted in decreased neuroblast development, as evidenced by decreased DCX expression and increased expression of platelet-derived growth factor α receptor (PDGFαR), a marker of oligodendrocyte precursors. In adult mice, Gro1 was induced in response to LPS treatment in male but not in female hippocampus, with a subsequent decrease in neurogenesis and activation of oligodendrocyte progenitors. No changes in neurogenesis were observed in females. Treatment with E2 blunted LPS-induced Gro1 in the male hippocampus. Conclusions Inflammation-induced Gro1 triggers neuroblast senescence, thus suppressing new neuron development in the hippocampus. Sex-dependent differences in Gro1 response are attributed to estradiol, which blunts these changes, protecting the female hippocampus from the deleterious effects of inflammation-induced Gro1 on neurogenesis. Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Svetlana Zonis [verfasserIn] Joshua J. Breunig [verfasserIn] Adam Mamelak [verfasserIn] Kolja Wawrowsky [verfasserIn] Catherine Bresee [verfasserIn] Nadiya Ginzburg [verfasserIn] Vera Chesnokova [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2018

Schlagwörter:	Chemokines Gro1 Hippocampus Neuronal progenitor cells Senescence LPS-induced inflammation

Übergeordnetes Werk:	In: Journal of Neuroinflammation - BMC, 2004, 15(2018), 1, Seite 17
Übergeordnetes Werk:	volume:15 ; year:2018 ; number:1 ; pages:17

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.1186/s12974-018-1298-y

Katalog-ID:	DOAJ011054425

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520			\|a Abstract Background Inflammation has been proposed to contribute to the decline in adult hippocampal neurogenesis. Proinflammatory cytokines activate transcription of chemokine growth-regulated oncogene α (Gro1) in human and murine hippocampal neuronal progenitor cells (NPC). The goal of this study was to investigate the effects of Gro1 on hippocampal neurogenesis in the presence of inflammation. Methods Human hippocampal NPC were transfected with lentivirus expressing Gro1, and murine NPC and hippocampal neuronal HT-22 cells were treated with Gro1 protein. A plasmid expressing mGro1 was electroporated in the hippocampus of newborn mice that were sacrificed 10 days later. Adult male and female mice were injected with lipopolysaccharide (LPS; 1 mg/kg, i.p in five daily injections) or normal saline. Adult male mice were implanted with pellets releasing 17-β estradiol (E2; 2.5 mg/pellet, 41.666 μg/day release) or placebo for 6 weeks and challenged with LPS or normal saline as above. In both experiments, mice were sacrificed 3 h after the last injection. Hippocampal markers of neurogenesis were assessed in vitro and in vivo by Western blot, real-time PCR, and immunohisto/cytochemistry. Results Gro1 induced premature senescence in NPC and HT-22 cells, activating senescence-associated β-galactosidase and the cell cycle inhibitor p16 and suppressing neuroblast proliferation and expression of doublecortin (DCX) and neuron-specific class III beta-tubulin (Tuj-1), both neuroblast markers, while promoting proliferation of neural glial antigen 2 (Ng2)-positive oligodendrocytes. Gro1 overexpression in the hippocampus of newborn mice resulted in decreased neuroblast development, as evidenced by decreased DCX expression and increased expression of platelet-derived growth factor α receptor (PDGFαR), a marker of oligodendrocyte precursors. In adult mice, Gro1 was induced in response to LPS treatment in male but not in female hippocampus, with a subsequent decrease in neurogenesis and activation of oligodendrocyte progenitors. No changes in neurogenesis were observed in females. Treatment with E2 blunted LPS-induced Gro1 in the male hippocampus. Conclusions Inflammation-induced Gro1 triggers neuroblast senescence, thus suppressing new neuron development in the hippocampus. Sex-dependent differences in Gro1 response are attributed to estradiol, which blunts these changes, protecting the female hippocampus from the deleterious effects of inflammation-induced Gro1 on neurogenesis.
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allfields	10.1186/s12974-018-1298-y doi (DE-627)DOAJ011054425 (DE-599)DOAJ75c5efb9ccf640958172bc61a700cb2b DE-627 ger DE-627 rakwb eng RC346-429 Svetlana Zonis verfasserin aut Inflammation-induced Gro1 triggers senescence in neuronal progenitors: effects of estradiol 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Inflammation has been proposed to contribute to the decline in adult hippocampal neurogenesis. Proinflammatory cytokines activate transcription of chemokine growth-regulated oncogene α (Gro1) in human and murine hippocampal neuronal progenitor cells (NPC). The goal of this study was to investigate the effects of Gro1 on hippocampal neurogenesis in the presence of inflammation. Methods Human hippocampal NPC were transfected with lentivirus expressing Gro1, and murine NPC and hippocampal neuronal HT-22 cells were treated with Gro1 protein. A plasmid expressing mGro1 was electroporated in the hippocampus of newborn mice that were sacrificed 10 days later. Adult male and female mice were injected with lipopolysaccharide (LPS; 1 mg/kg, i.p in five daily injections) or normal saline. Adult male mice were implanted with pellets releasing 17-β estradiol (E2; 2.5 mg/pellet, 41.666 μg/day release) or placebo for 6 weeks and challenged with LPS or normal saline as above. In both experiments, mice were sacrificed 3 h after the last injection. Hippocampal markers of neurogenesis were assessed in vitro and in vivo by Western blot, real-time PCR, and immunohisto/cytochemistry. Results Gro1 induced premature senescence in NPC and HT-22 cells, activating senescence-associated β-galactosidase and the cell cycle inhibitor p16 and suppressing neuroblast proliferation and expression of doublecortin (DCX) and neuron-specific class III beta-tubulin (Tuj-1), both neuroblast markers, while promoting proliferation of neural glial antigen 2 (Ng2)-positive oligodendrocytes. Gro1 overexpression in the hippocampus of newborn mice resulted in decreased neuroblast development, as evidenced by decreased DCX expression and increased expression of platelet-derived growth factor α receptor (PDGFαR), a marker of oligodendrocyte precursors. In adult mice, Gro1 was induced in response to LPS treatment in male but not in female hippocampus, with a subsequent decrease in neurogenesis and activation of oligodendrocyte progenitors. No changes in neurogenesis were observed in females. Treatment with E2 blunted LPS-induced Gro1 in the male hippocampus. Conclusions Inflammation-induced Gro1 triggers neuroblast senescence, thus suppressing new neuron development in the hippocampus. Sex-dependent differences in Gro1 response are attributed to estradiol, which blunts these changes, protecting the female hippocampus from the deleterious effects of inflammation-induced Gro1 on neurogenesis. Chemokines Gro1 Hippocampus Neuronal progenitor cells Senescence LPS-induced inflammation Neurology. Diseases of the nervous system Joshua J. Breunig verfasserin aut Adam Mamelak verfasserin aut Kolja Wawrowsky verfasserin aut Catherine Bresee verfasserin aut Nadiya Ginzburg verfasserin aut Vera Chesnokova verfasserin aut In Journal of Neuroinflammation BMC, 2004 15(2018), 1, Seite 17 (DE-627)391784781 (DE-600)2156455-3 17422094 nnns volume:15 year:2018 number:1 pages:17 https://doi.org/10.1186/s12974-018-1298-y kostenfrei https://doaj.org/article/75c5efb9ccf640958172bc61a700cb2b kostenfrei http://link.springer.com/article/10.1186/s12974-018-1298-y kostenfrei https://doaj.org/toc/1742-2094 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 15 2018 1 17
spelling	10.1186/s12974-018-1298-y doi (DE-627)DOAJ011054425 (DE-599)DOAJ75c5efb9ccf640958172bc61a700cb2b DE-627 ger DE-627 rakwb eng RC346-429 Svetlana Zonis verfasserin aut Inflammation-induced Gro1 triggers senescence in neuronal progenitors: effects of estradiol 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Inflammation has been proposed to contribute to the decline in adult hippocampal neurogenesis. Proinflammatory cytokines activate transcription of chemokine growth-regulated oncogene α (Gro1) in human and murine hippocampal neuronal progenitor cells (NPC). The goal of this study was to investigate the effects of Gro1 on hippocampal neurogenesis in the presence of inflammation. Methods Human hippocampal NPC were transfected with lentivirus expressing Gro1, and murine NPC and hippocampal neuronal HT-22 cells were treated with Gro1 protein. A plasmid expressing mGro1 was electroporated in the hippocampus of newborn mice that were sacrificed 10 days later. Adult male and female mice were injected with lipopolysaccharide (LPS; 1 mg/kg, i.p in five daily injections) or normal saline. Adult male mice were implanted with pellets releasing 17-β estradiol (E2; 2.5 mg/pellet, 41.666 μg/day release) or placebo for 6 weeks and challenged with LPS or normal saline as above. In both experiments, mice were sacrificed 3 h after the last injection. Hippocampal markers of neurogenesis were assessed in vitro and in vivo by Western blot, real-time PCR, and immunohisto/cytochemistry. Results Gro1 induced premature senescence in NPC and HT-22 cells, activating senescence-associated β-galactosidase and the cell cycle inhibitor p16 and suppressing neuroblast proliferation and expression of doublecortin (DCX) and neuron-specific class III beta-tubulin (Tuj-1), both neuroblast markers, while promoting proliferation of neural glial antigen 2 (Ng2)-positive oligodendrocytes. Gro1 overexpression in the hippocampus of newborn mice resulted in decreased neuroblast development, as evidenced by decreased DCX expression and increased expression of platelet-derived growth factor α receptor (PDGFαR), a marker of oligodendrocyte precursors. In adult mice, Gro1 was induced in response to LPS treatment in male but not in female hippocampus, with a subsequent decrease in neurogenesis and activation of oligodendrocyte progenitors. No changes in neurogenesis were observed in females. Treatment with E2 blunted LPS-induced Gro1 in the male hippocampus. Conclusions Inflammation-induced Gro1 triggers neuroblast senescence, thus suppressing new neuron development in the hippocampus. Sex-dependent differences in Gro1 response are attributed to estradiol, which blunts these changes, protecting the female hippocampus from the deleterious effects of inflammation-induced Gro1 on neurogenesis. Chemokines Gro1 Hippocampus Neuronal progenitor cells Senescence LPS-induced inflammation Neurology. Diseases of the nervous system Joshua J. Breunig verfasserin aut Adam Mamelak verfasserin aut Kolja Wawrowsky verfasserin aut Catherine Bresee verfasserin aut Nadiya Ginzburg verfasserin aut Vera Chesnokova verfasserin aut In Journal of Neuroinflammation BMC, 2004 15(2018), 1, Seite 17 (DE-627)391784781 (DE-600)2156455-3 17422094 nnns volume:15 year:2018 number:1 pages:17 https://doi.org/10.1186/s12974-018-1298-y kostenfrei https://doaj.org/article/75c5efb9ccf640958172bc61a700cb2b kostenfrei http://link.springer.com/article/10.1186/s12974-018-1298-y kostenfrei https://doaj.org/toc/1742-2094 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 15 2018 1 17
allfields_unstemmed	10.1186/s12974-018-1298-y doi (DE-627)DOAJ011054425 (DE-599)DOAJ75c5efb9ccf640958172bc61a700cb2b DE-627 ger DE-627 rakwb eng RC346-429 Svetlana Zonis verfasserin aut Inflammation-induced Gro1 triggers senescence in neuronal progenitors: effects of estradiol 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Inflammation has been proposed to contribute to the decline in adult hippocampal neurogenesis. Proinflammatory cytokines activate transcription of chemokine growth-regulated oncogene α (Gro1) in human and murine hippocampal neuronal progenitor cells (NPC). The goal of this study was to investigate the effects of Gro1 on hippocampal neurogenesis in the presence of inflammation. Methods Human hippocampal NPC were transfected with lentivirus expressing Gro1, and murine NPC and hippocampal neuronal HT-22 cells were treated with Gro1 protein. A plasmid expressing mGro1 was electroporated in the hippocampus of newborn mice that were sacrificed 10 days later. Adult male and female mice were injected with lipopolysaccharide (LPS; 1 mg/kg, i.p in five daily injections) or normal saline. Adult male mice were implanted with pellets releasing 17-β estradiol (E2; 2.5 mg/pellet, 41.666 μg/day release) or placebo for 6 weeks and challenged with LPS or normal saline as above. In both experiments, mice were sacrificed 3 h after the last injection. Hippocampal markers of neurogenesis were assessed in vitro and in vivo by Western blot, real-time PCR, and immunohisto/cytochemistry. Results Gro1 induced premature senescence in NPC and HT-22 cells, activating senescence-associated β-galactosidase and the cell cycle inhibitor p16 and suppressing neuroblast proliferation and expression of doublecortin (DCX) and neuron-specific class III beta-tubulin (Tuj-1), both neuroblast markers, while promoting proliferation of neural glial antigen 2 (Ng2)-positive oligodendrocytes. Gro1 overexpression in the hippocampus of newborn mice resulted in decreased neuroblast development, as evidenced by decreased DCX expression and increased expression of platelet-derived growth factor α receptor (PDGFαR), a marker of oligodendrocyte precursors. In adult mice, Gro1 was induced in response to LPS treatment in male but not in female hippocampus, with a subsequent decrease in neurogenesis and activation of oligodendrocyte progenitors. No changes in neurogenesis were observed in females. Treatment with E2 blunted LPS-induced Gro1 in the male hippocampus. Conclusions Inflammation-induced Gro1 triggers neuroblast senescence, thus suppressing new neuron development in the hippocampus. Sex-dependent differences in Gro1 response are attributed to estradiol, which blunts these changes, protecting the female hippocampus from the deleterious effects of inflammation-induced Gro1 on neurogenesis. Chemokines Gro1 Hippocampus Neuronal progenitor cells Senescence LPS-induced inflammation Neurology. Diseases of the nervous system Joshua J. Breunig verfasserin aut Adam Mamelak verfasserin aut Kolja Wawrowsky verfasserin aut Catherine Bresee verfasserin aut Nadiya Ginzburg verfasserin aut Vera Chesnokova verfasserin aut In Journal of Neuroinflammation BMC, 2004 15(2018), 1, Seite 17 (DE-627)391784781 (DE-600)2156455-3 17422094 nnns volume:15 year:2018 number:1 pages:17 https://doi.org/10.1186/s12974-018-1298-y kostenfrei https://doaj.org/article/75c5efb9ccf640958172bc61a700cb2b kostenfrei http://link.springer.com/article/10.1186/s12974-018-1298-y kostenfrei https://doaj.org/toc/1742-2094 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 15 2018 1 17
allfieldsGer	10.1186/s12974-018-1298-y doi (DE-627)DOAJ011054425 (DE-599)DOAJ75c5efb9ccf640958172bc61a700cb2b DE-627 ger DE-627 rakwb eng RC346-429 Svetlana Zonis verfasserin aut Inflammation-induced Gro1 triggers senescence in neuronal progenitors: effects of estradiol 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Inflammation has been proposed to contribute to the decline in adult hippocampal neurogenesis. Proinflammatory cytokines activate transcription of chemokine growth-regulated oncogene α (Gro1) in human and murine hippocampal neuronal progenitor cells (NPC). The goal of this study was to investigate the effects of Gro1 on hippocampal neurogenesis in the presence of inflammation. Methods Human hippocampal NPC were transfected with lentivirus expressing Gro1, and murine NPC and hippocampal neuronal HT-22 cells were treated with Gro1 protein. A plasmid expressing mGro1 was electroporated in the hippocampus of newborn mice that were sacrificed 10 days later. Adult male and female mice were injected with lipopolysaccharide (LPS; 1 mg/kg, i.p in five daily injections) or normal saline. Adult male mice were implanted with pellets releasing 17-β estradiol (E2; 2.5 mg/pellet, 41.666 μg/day release) or placebo for 6 weeks and challenged with LPS or normal saline as above. In both experiments, mice were sacrificed 3 h after the last injection. Hippocampal markers of neurogenesis were assessed in vitro and in vivo by Western blot, real-time PCR, and immunohisto/cytochemistry. Results Gro1 induced premature senescence in NPC and HT-22 cells, activating senescence-associated β-galactosidase and the cell cycle inhibitor p16 and suppressing neuroblast proliferation and expression of doublecortin (DCX) and neuron-specific class III beta-tubulin (Tuj-1), both neuroblast markers, while promoting proliferation of neural glial antigen 2 (Ng2)-positive oligodendrocytes. Gro1 overexpression in the hippocampus of newborn mice resulted in decreased neuroblast development, as evidenced by decreased DCX expression and increased expression of platelet-derived growth factor α receptor (PDGFαR), a marker of oligodendrocyte precursors. In adult mice, Gro1 was induced in response to LPS treatment in male but not in female hippocampus, with a subsequent decrease in neurogenesis and activation of oligodendrocyte progenitors. No changes in neurogenesis were observed in females. Treatment with E2 blunted LPS-induced Gro1 in the male hippocampus. Conclusions Inflammation-induced Gro1 triggers neuroblast senescence, thus suppressing new neuron development in the hippocampus. Sex-dependent differences in Gro1 response are attributed to estradiol, which blunts these changes, protecting the female hippocampus from the deleterious effects of inflammation-induced Gro1 on neurogenesis. Chemokines Gro1 Hippocampus Neuronal progenitor cells Senescence LPS-induced inflammation Neurology. Diseases of the nervous system Joshua J. Breunig verfasserin aut Adam Mamelak verfasserin aut Kolja Wawrowsky verfasserin aut Catherine Bresee verfasserin aut Nadiya Ginzburg verfasserin aut Vera Chesnokova verfasserin aut In Journal of Neuroinflammation BMC, 2004 15(2018), 1, Seite 17 (DE-627)391784781 (DE-600)2156455-3 17422094 nnns volume:15 year:2018 number:1 pages:17 https://doi.org/10.1186/s12974-018-1298-y kostenfrei https://doaj.org/article/75c5efb9ccf640958172bc61a700cb2b kostenfrei http://link.springer.com/article/10.1186/s12974-018-1298-y kostenfrei https://doaj.org/toc/1742-2094 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 15 2018 1 17
allfieldsSound	10.1186/s12974-018-1298-y doi (DE-627)DOAJ011054425 (DE-599)DOAJ75c5efb9ccf640958172bc61a700cb2b DE-627 ger DE-627 rakwb eng RC346-429 Svetlana Zonis verfasserin aut Inflammation-induced Gro1 triggers senescence in neuronal progenitors: effects of estradiol 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Inflammation has been proposed to contribute to the decline in adult hippocampal neurogenesis. Proinflammatory cytokines activate transcription of chemokine growth-regulated oncogene α (Gro1) in human and murine hippocampal neuronal progenitor cells (NPC). The goal of this study was to investigate the effects of Gro1 on hippocampal neurogenesis in the presence of inflammation. Methods Human hippocampal NPC were transfected with lentivirus expressing Gro1, and murine NPC and hippocampal neuronal HT-22 cells were treated with Gro1 protein. A plasmid expressing mGro1 was electroporated in the hippocampus of newborn mice that were sacrificed 10 days later. Adult male and female mice were injected with lipopolysaccharide (LPS; 1 mg/kg, i.p in five daily injections) or normal saline. Adult male mice were implanted with pellets releasing 17-β estradiol (E2; 2.5 mg/pellet, 41.666 μg/day release) or placebo for 6 weeks and challenged with LPS or normal saline as above. In both experiments, mice were sacrificed 3 h after the last injection. Hippocampal markers of neurogenesis were assessed in vitro and in vivo by Western blot, real-time PCR, and immunohisto/cytochemistry. Results Gro1 induced premature senescence in NPC and HT-22 cells, activating senescence-associated β-galactosidase and the cell cycle inhibitor p16 and suppressing neuroblast proliferation and expression of doublecortin (DCX) and neuron-specific class III beta-tubulin (Tuj-1), both neuroblast markers, while promoting proliferation of neural glial antigen 2 (Ng2)-positive oligodendrocytes. Gro1 overexpression in the hippocampus of newborn mice resulted in decreased neuroblast development, as evidenced by decreased DCX expression and increased expression of platelet-derived growth factor α receptor (PDGFαR), a marker of oligodendrocyte precursors. In adult mice, Gro1 was induced in response to LPS treatment in male but not in female hippocampus, with a subsequent decrease in neurogenesis and activation of oligodendrocyte progenitors. No changes in neurogenesis were observed in females. Treatment with E2 blunted LPS-induced Gro1 in the male hippocampus. Conclusions Inflammation-induced Gro1 triggers neuroblast senescence, thus suppressing new neuron development in the hippocampus. Sex-dependent differences in Gro1 response are attributed to estradiol, which blunts these changes, protecting the female hippocampus from the deleterious effects of inflammation-induced Gro1 on neurogenesis. Chemokines Gro1 Hippocampus Neuronal progenitor cells Senescence LPS-induced inflammation Neurology. Diseases of the nervous system Joshua J. Breunig verfasserin aut Adam Mamelak verfasserin aut Kolja Wawrowsky verfasserin aut Catherine Bresee verfasserin aut Nadiya Ginzburg verfasserin aut Vera Chesnokova verfasserin aut In Journal of Neuroinflammation BMC, 2004 15(2018), 1, Seite 17 (DE-627)391784781 (DE-600)2156455-3 17422094 nnns volume:15 year:2018 number:1 pages:17 https://doi.org/10.1186/s12974-018-1298-y kostenfrei https://doaj.org/article/75c5efb9ccf640958172bc61a700cb2b kostenfrei http://link.springer.com/article/10.1186/s12974-018-1298-y kostenfrei https://doaj.org/toc/1742-2094 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 15 2018 1 17
language	English
source	In Journal of Neuroinflammation 15(2018), 1, Seite 17 volume:15 year:2018 number:1 pages:17
sourceStr	In Journal of Neuroinflammation 15(2018), 1, Seite 17 volume:15 year:2018 number:1 pages:17
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Chemokines Gro1 Hippocampus Neuronal progenitor cells Senescence LPS-induced inflammation Neurology. Diseases of the nervous system
isfreeaccess_bool	true
container_title	Journal of Neuroinflammation
authorswithroles_txt_mv	Svetlana Zonis @@aut@@ Joshua J. Breunig @@aut@@ Adam Mamelak @@aut@@ Kolja Wawrowsky @@aut@@ Catherine Bresee @@aut@@ Nadiya Ginzburg @@aut@@ Vera Chesnokova @@aut@@
publishDateDaySort_date	2018-01-01T00:00:00Z
hierarchy_top_id	391784781
id	DOAJ011054425
language_de	englisch
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Proinflammatory cytokines activate transcription of chemokine growth-regulated oncogene α (Gro1) in human and murine hippocampal neuronal progenitor cells (NPC). The goal of this study was to investigate the effects of Gro1 on hippocampal neurogenesis in the presence of inflammation. Methods Human hippocampal NPC were transfected with lentivirus expressing Gro1, and murine NPC and hippocampal neuronal HT-22 cells were treated with Gro1 protein. A plasmid expressing mGro1 was electroporated in the hippocampus of newborn mice that were sacrificed 10 days later. Adult male and female mice were injected with lipopolysaccharide (LPS; 1 mg/kg, i.p in five daily injections) or normal saline. Adult male mice were implanted with pellets releasing 17-β estradiol (E2; 2.5 mg/pellet, 41.666 μg/day release) or placebo for 6 weeks and challenged with LPS or normal saline as above. In both experiments, mice were sacrificed 3 h after the last injection. Hippocampal markers of neurogenesis were assessed in vitro and in vivo by Western blot, real-time PCR, and immunohisto/cytochemistry. Results Gro1 induced premature senescence in NPC and HT-22 cells, activating senescence-associated β-galactosidase and the cell cycle inhibitor p16 and suppressing neuroblast proliferation and expression of doublecortin (DCX) and neuron-specific class III beta-tubulin (Tuj-1), both neuroblast markers, while promoting proliferation of neural glial antigen 2 (Ng2)-positive oligodendrocytes. Gro1 overexpression in the hippocampus of newborn mice resulted in decreased neuroblast development, as evidenced by decreased DCX expression and increased expression of platelet-derived growth factor α receptor (PDGFαR), a marker of oligodendrocyte precursors. In adult mice, Gro1 was induced in response to LPS treatment in male but not in female hippocampus, with a subsequent decrease in neurogenesis and activation of oligodendrocyte progenitors. No changes in neurogenesis were observed in females. Treatment with E2 blunted LPS-induced Gro1 in the male hippocampus. Conclusions Inflammation-induced Gro1 triggers neuroblast senescence, thus suppressing new neuron development in the hippocampus. 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callnumber-first	R - Medicine
author	Svetlana Zonis
spellingShingle	Svetlana Zonis misc RC346-429 misc Chemokines misc Gro1 misc Hippocampus misc Neuronal progenitor cells misc Senescence misc LPS-induced inflammation misc Neurology. Diseases of the nervous system Inflammation-induced Gro1 triggers senescence in neuronal progenitors: effects of estradiol
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topic_title	RC346-429 Inflammation-induced Gro1 triggers senescence in neuronal progenitors: effects of estradiol Chemokines Gro1 Hippocampus Neuronal progenitor cells Senescence LPS-induced inflammation
topic	misc RC346-429 misc Chemokines misc Gro1 misc Hippocampus misc Neuronal progenitor cells misc Senescence misc LPS-induced inflammation misc Neurology. Diseases of the nervous system
topic_unstemmed	misc RC346-429 misc Chemokines misc Gro1 misc Hippocampus misc Neuronal progenitor cells misc Senescence misc LPS-induced inflammation misc Neurology. Diseases of the nervous system
topic_browse	misc RC346-429 misc Chemokines misc Gro1 misc Hippocampus misc Neuronal progenitor cells misc Senescence misc LPS-induced inflammation misc Neurology. Diseases of the nervous system
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title	Inflammation-induced Gro1 triggers senescence in neuronal progenitors: effects of estradiol
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title_full	Inflammation-induced Gro1 triggers senescence in neuronal progenitors: effects of estradiol
author_sort	Svetlana Zonis
journal	Journal of Neuroinflammation
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author_browse	Svetlana Zonis Joshua J. Breunig Adam Mamelak Kolja Wawrowsky Catherine Bresee Nadiya Ginzburg Vera Chesnokova
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class	RC346-429
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doi_str_mv	10.1186/s12974-018-1298-y
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title_sort	inflammation-induced gro1 triggers senescence in neuronal progenitors: effects of estradiol
callnumber	RC346-429
title_auth	Inflammation-induced Gro1 triggers senescence in neuronal progenitors: effects of estradiol
abstract	Abstract Background Inflammation has been proposed to contribute to the decline in adult hippocampal neurogenesis. Proinflammatory cytokines activate transcription of chemokine growth-regulated oncogene α (Gro1) in human and murine hippocampal neuronal progenitor cells (NPC). The goal of this study was to investigate the effects of Gro1 on hippocampal neurogenesis in the presence of inflammation. Methods Human hippocampal NPC were transfected with lentivirus expressing Gro1, and murine NPC and hippocampal neuronal HT-22 cells were treated with Gro1 protein. A plasmid expressing mGro1 was electroporated in the hippocampus of newborn mice that were sacrificed 10 days later. Adult male and female mice were injected with lipopolysaccharide (LPS; 1 mg/kg, i.p in five daily injections) or normal saline. Adult male mice were implanted with pellets releasing 17-β estradiol (E2; 2.5 mg/pellet, 41.666 μg/day release) or placebo for 6 weeks and challenged with LPS or normal saline as above. In both experiments, mice were sacrificed 3 h after the last injection. Hippocampal markers of neurogenesis were assessed in vitro and in vivo by Western blot, real-time PCR, and immunohisto/cytochemistry. Results Gro1 induced premature senescence in NPC and HT-22 cells, activating senescence-associated β-galactosidase and the cell cycle inhibitor p16 and suppressing neuroblast proliferation and expression of doublecortin (DCX) and neuron-specific class III beta-tubulin (Tuj-1), both neuroblast markers, while promoting proliferation of neural glial antigen 2 (Ng2)-positive oligodendrocytes. Gro1 overexpression in the hippocampus of newborn mice resulted in decreased neuroblast development, as evidenced by decreased DCX expression and increased expression of platelet-derived growth factor α receptor (PDGFαR), a marker of oligodendrocyte precursors. In adult mice, Gro1 was induced in response to LPS treatment in male but not in female hippocampus, with a subsequent decrease in neurogenesis and activation of oligodendrocyte progenitors. No changes in neurogenesis were observed in females. Treatment with E2 blunted LPS-induced Gro1 in the male hippocampus. Conclusions Inflammation-induced Gro1 triggers neuroblast senescence, thus suppressing new neuron development in the hippocampus. Sex-dependent differences in Gro1 response are attributed to estradiol, which blunts these changes, protecting the female hippocampus from the deleterious effects of inflammation-induced Gro1 on neurogenesis.
abstractGer	Abstract Background Inflammation has been proposed to contribute to the decline in adult hippocampal neurogenesis. Proinflammatory cytokines activate transcription of chemokine growth-regulated oncogene α (Gro1) in human and murine hippocampal neuronal progenitor cells (NPC). The goal of this study was to investigate the effects of Gro1 on hippocampal neurogenesis in the presence of inflammation. Methods Human hippocampal NPC were transfected with lentivirus expressing Gro1, and murine NPC and hippocampal neuronal HT-22 cells were treated with Gro1 protein. A plasmid expressing mGro1 was electroporated in the hippocampus of newborn mice that were sacrificed 10 days later. Adult male and female mice were injected with lipopolysaccharide (LPS; 1 mg/kg, i.p in five daily injections) or normal saline. Adult male mice were implanted with pellets releasing 17-β estradiol (E2; 2.5 mg/pellet, 41.666 μg/day release) or placebo for 6 weeks and challenged with LPS or normal saline as above. In both experiments, mice were sacrificed 3 h after the last injection. Hippocampal markers of neurogenesis were assessed in vitro and in vivo by Western blot, real-time PCR, and immunohisto/cytochemistry. Results Gro1 induced premature senescence in NPC and HT-22 cells, activating senescence-associated β-galactosidase and the cell cycle inhibitor p16 and suppressing neuroblast proliferation and expression of doublecortin (DCX) and neuron-specific class III beta-tubulin (Tuj-1), both neuroblast markers, while promoting proliferation of neural glial antigen 2 (Ng2)-positive oligodendrocytes. Gro1 overexpression in the hippocampus of newborn mice resulted in decreased neuroblast development, as evidenced by decreased DCX expression and increased expression of platelet-derived growth factor α receptor (PDGFαR), a marker of oligodendrocyte precursors. In adult mice, Gro1 was induced in response to LPS treatment in male but not in female hippocampus, with a subsequent decrease in neurogenesis and activation of oligodendrocyte progenitors. No changes in neurogenesis were observed in females. Treatment with E2 blunted LPS-induced Gro1 in the male hippocampus. Conclusions Inflammation-induced Gro1 triggers neuroblast senescence, thus suppressing new neuron development in the hippocampus. Sex-dependent differences in Gro1 response are attributed to estradiol, which blunts these changes, protecting the female hippocampus from the deleterious effects of inflammation-induced Gro1 on neurogenesis.
abstract_unstemmed	Abstract Background Inflammation has been proposed to contribute to the decline in adult hippocampal neurogenesis. Proinflammatory cytokines activate transcription of chemokine growth-regulated oncogene α (Gro1) in human and murine hippocampal neuronal progenitor cells (NPC). The goal of this study was to investigate the effects of Gro1 on hippocampal neurogenesis in the presence of inflammation. Methods Human hippocampal NPC were transfected with lentivirus expressing Gro1, and murine NPC and hippocampal neuronal HT-22 cells were treated with Gro1 protein. A plasmid expressing mGro1 was electroporated in the hippocampus of newborn mice that were sacrificed 10 days later. Adult male and female mice were injected with lipopolysaccharide (LPS; 1 mg/kg, i.p in five daily injections) or normal saline. Adult male mice were implanted with pellets releasing 17-β estradiol (E2; 2.5 mg/pellet, 41.666 μg/day release) or placebo for 6 weeks and challenged with LPS or normal saline as above. In both experiments, mice were sacrificed 3 h after the last injection. Hippocampal markers of neurogenesis were assessed in vitro and in vivo by Western blot, real-time PCR, and immunohisto/cytochemistry. Results Gro1 induced premature senescence in NPC and HT-22 cells, activating senescence-associated β-galactosidase and the cell cycle inhibitor p16 and suppressing neuroblast proliferation and expression of doublecortin (DCX) and neuron-specific class III beta-tubulin (Tuj-1), both neuroblast markers, while promoting proliferation of neural glial antigen 2 (Ng2)-positive oligodendrocytes. Gro1 overexpression in the hippocampus of newborn mice resulted in decreased neuroblast development, as evidenced by decreased DCX expression and increased expression of platelet-derived growth factor α receptor (PDGFαR), a marker of oligodendrocyte precursors. In adult mice, Gro1 was induced in response to LPS treatment in male but not in female hippocampus, with a subsequent decrease in neurogenesis and activation of oligodendrocyte progenitors. No changes in neurogenesis were observed in females. Treatment with E2 blunted LPS-induced Gro1 in the male hippocampus. Conclusions Inflammation-induced Gro1 triggers neuroblast senescence, thus suppressing new neuron development in the hippocampus. Sex-dependent differences in Gro1 response are attributed to estradiol, which blunts these changes, protecting the female hippocampus from the deleterious effects of inflammation-induced Gro1 on neurogenesis.
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title_short	Inflammation-induced Gro1 triggers senescence in neuronal progenitors: effects of estradiol
url	https://doi.org/10.1186/s12974-018-1298-y https://doaj.org/article/75c5efb9ccf640958172bc61a700cb2b http://link.springer.com/article/10.1186/s12974-018-1298-y https://doaj.org/toc/1742-2094
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