Estradiol attenuates hyperoxia‐induced cell death in the developing white matter

Gerstner, Bettina; Sifringer, Marco; Dzietko, Mark; Schüller, Andreas; Lee, Joon; Simons, Sinno; Obladen, Michael; Volpe, Joseph J.; Rosenberg, Paul A.; Felderhoff‐Mueser, Ursula

doi:10.1002/ana.21118

Cited by 82 publications

(75 citation statements)

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“…Activation of MAPK and Akt by phosphorylation inhibits apoptosis (Cui et al, 2005). Indeed, 17b-estradiol protected OLs against hyperoxia-induced injury and prevented decreases in phosphorylated forms of MAPK and Akt after both in vitro and in vivo treatment (Gerstner et al, 2007). Activation of GSK-3b by phosphorylation is also involved in recovery of OLs from stress (Goldbaum and Richter-Landsberg, 2002).…”

Section: Discussionmentioning

confidence: 99%

“…However, the function of these extranuclear receptors in OLs is not known. Prolonged exposure to estradiol stimulates proliferation and differentiation of OLs (Jung-Testas et al, 1992;Marin-Husstege et al, 2004;Zhang et al, 2004), and protects them from cell death because of hyperoxia or cytotoxic agents (Gerstner et al, 2007;Takao et al, 2004), but these effects may have been mediated through the nuclear receptor. To provide evidence for a role for a membrane ER in rapid signaling in OLs, we have investigated the effect of both 17a-and 17b-estradiol on short-term activation of several signaling pathways known to be involved in development of myelinating cells, involving MAPK, Akt, and GSK-3b (Cui et al, 2005;Khorchid et al, 1999;Ogata et al, 2004;Palacios et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

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The localization and non‐genomic function of the membrane‐associated estrogen receptor in oligodendrocytes

Hirahara

Matsuda

Gao

et al. 2008

Glia

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There is general acceptance that the estrogen receptor can act as a transcription factor. However, estrogens can also bind to receptors that are located at the plasma membrane and stimulate rapid intracellular signaling processes. We recently showed that a membrane-associated estrogen receptor (mER) is present within myelin and at the oligodendrocyte (OL) plasma membrane. To understand the physiological function of mER in OLs, we investigated its cellular localization and involvement in rapid signaling in CG4 cells and OL primary cultures. An ERa was expressed along the lacy network of veins in the membrane sheets and in the perikaryon and nucleus in OLs. ERb was located in the nucleus, and to a lesser extent along the veins. The expression of ERa and ERb in OL membranes was confirmed by Western analysis of isolated membranes. OL membranes mainly had truncated forms of ERa, 53 and 50 kDa, in addition to some 65 kDa form, whereas ERb was a 54 kDa form. CG4 cells and OLs were pulsed with 17a-and 17b-estradiol for various times and the total lysates were analyzed for phosphorylated kinases. Both 17a-and 17b-estradiol elicited rapid phosphorylation of p42/44MAPK, Akt, and GSK-3b within 8 min. This rapid signaling is consistent with estradiol ligation of a membrane form of ER. Since 17a-estradiol is produced at higher concentrations than 17b-estradiol in the brain of both sexes, signaling via 17a-estradiol-liganded mER may have an important function in OLs. V V C

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The localization and non‐genomic function of the membrane‐associated estrogen receptor in oligodendrocytes

Hirahara

Matsuda

Gao

et al. 2008

Glia

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“…Primarily affected brain regions include the cortex, caudate nucleus, thalamus and white matter tracts. Exposure of immature rodents to hyperoxia triggers diffuse neuronal and oligodendrocyte cell death and is associated with oxidative stress, nitrative stress, impairment of neurotrophin signaling and upregulation of proinflammatory cytokines [2,10] . Our recent data suggests that exposure of P6 rodents to hyperoxia over a period of 24 h increased the rate of cell death in the developing rat brain acutely.…”

Section: Discussionmentioning

confidence: 99%

“…These regions include cortical areas, basal ganglia, hypothalamus, hippocampus and white matter tracts. On a molecular level, cell death is accompanied by induction of proapoptotic pathways [2,3] , oxidative stress [4,5] and a reduction in neurotrophindependent pathways, including that of Jak2/extracellular signal-regulated kinase (ERK) [1,2] . Hyperoxia exposure in the first week of rodent life also causes microvascular degeneration and altered brain mass and function at the age of 30 days [6] .…”

Section: Introductionmentioning

confidence: 99%

Erythropoietin Attenuates Hyperoxia-Induced Cell Death by Modulation of Inflammatory Mediators and Matrix Metalloproteinases

Sifringer¹,

Genz²,

Brait³

et al. 2009

Dev Neurosci

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Oxygen toxicity appears to contribute to the pathogenesis of adverse neurological outcome in survivors of preterm birth. In infant rodent brains, hyperoxia triggers widespread apoptotic neurodegeneration, induces proinflammatory cytokines and inhibits growth factor signaling cascades. Since a tissue-protective effect has been observed for recombinant erythropoietin (rEpo), we hypothesized that rEpo would influence the expression of proinflammatory cytokines and matrix metalloproteinase (MMP)-2 and MMP-9. Six-day-old Wistar rats were exposed to 80% oxygen for 2–48 h and received 20,000 IU rEpo i.p. Sex-matched littermates kept in room air and injected with normal saline or rEpo served as controls. Treatment with rEpo significantly reduced hyperoxia-induced upregulation of the proinflammatory cytokines IL-1β and IL-18 in infant rodent brains on the mRNA and protein levels. In parallel, gelatin zymography in hyperoxia-treated immature rat brains revealed an upregulation of active MMP-2 which was reduced by concomitant rEpo treatment. Furthermore, hyperoxia induced upregulation of MMP-9 following 12 h of oxygen exposure and this was attenuated by rEpo treatment. Our results suggest that rEpo generates its protective effect against oxygen toxicity through a reduction of proinflammatory mediator levels.

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“…Эстрогены проявляют защитные эффекты в моделях токсического и ишемического повреждения ЦНС: при глутаматной эксайтотоксичности (мембранные, РЭα, снижение уровня mGluR1 [50]); при аутоиммунном энце-фаломиелите (GPER1) [51]; при рассеянном склерозе [52]; при каинатной, метамфетаминовой, алкогольной и глюкокортикоидной токсичности [53]; при колхици-новом повреждении мозга, гипоксическом повреждении развивающихся олигодендроцитов (РЭα и РЭβ) [54]. Так, высокий уровень экзогенных и эндогенных эстро-генов может задерживать развитие симптомов рассеян-ного склероза [52].…”

Section: нейропротекторная активность эстрадиолаunclassified

Estrogens and Brain

et al. 2012

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Estrogens and brain Recent data upon molecular mechanisms of pleiotropic action of estrogens in human brain is presented in the article. Given detailed descriptions of properties of classical and membrane bound estradiol receptors, that maintain gene expression regulation, modulation of neurotransmittent systems and signal cascade activation in neuronal cells. Data upon regional distribution of estradiol receptor subtypes in the brain, their participation in main cell population function control (including progenitor cells) is given. Special attention is paid to estrogen participation in neurogenesis, inflammationand apoptosis regulation in central nervous system; in the control of formation and functioning of cerebral vessels.

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Estradiol attenuates hyperoxia‐induced cell death in the developing white matter

Abstract: These results suggest a possible role for estrogens in the prevention of neonatal oxygen-induced white matter injury.

Cited by 82 publications

References 59 publications

The localization and non‐genomic function of the membrane‐associated estrogen receptor in oligodendrocytes

The localization and non‐genomic function of the membrane‐associated estrogen receptor in oligodendrocytes

Erythropoietin Attenuates Hyperoxia-Induced Cell Death by Modulation of Inflammatory Mediators and Matrix Metalloproteinases

Estrogens and Brain

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