Abstract:
:Neuronal cell death caused by pathophysiological over-activation of glutamate receptors and the subsequent CaII overloading, has been implicated in neurodegeneration after stroke, cerebral trauma and epileptic seizures. Recent findings suggest that certain progesterone metabolites (neurosteroids) such as allopregnanolone and dehydroepiandrosterone can protect neuronal cells from such insults. In the present study, murine P19 cells were induced to differentiate into postmitotic neurons expressing specific neuronal markers, including GABA(A) and NMDA receptors. Activation of NMDA receptors in P19-N neurons resulted in excitotoxic cell death, which involved suppression of the phosphorylation of the survival kinase PKB/Akt. Allopregnanolone and DHEA induced a rapid and prolonged phosphorylation of the Akt kinase and they were able to reverse the NMDA-induced suppression of the PI3-K/Akt pathway. The specificity of the neuroprotective effects of these neurosteroids was confirmed by the phosphatidylinositol 3-kinase (PI3-K) inhibitor wortmannin, as well as by the GABA(A) receptor antagonist, bicuculline. The neurotoxic effect of NMDA on P19-N neurons was directly correlated with increased CaII entry, since the addition of EGTA or BAPTA-AM, significantly suppressed the NMDA-induced decrease of phospho-Akt and subsequent neuronal death. These results suggest that neurosteroids are able to act as survival factors on P19-N neurons, promoting the activation of the PI3-K/Akt pathway through a calcium-entry dependent mechanism.
journal_name
Neurotox Resjournal_title
Neurotoxicity researchauthors
Xilouri M,Papazafiri Pdoi
10.1007/BF03033504subject
Has Abstractpub_date
2008-05-01 00:00:00pages
209-19issue
3-4eissn
1029-8428issn
1476-3524journal_volume
13pub_type
杂志文章abstract::There has been a growing recognition of the role of neuroinflammation caused by microglia-exaggerated release of inflammatory mediators in the pathogenesis of Parkinson's disease (PD). Pituitary adenylate cyclase activating polypeptide (PACAP) is an endogenous 38 amino acid containing neuropeptide that has been shown ...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/s12640-014-9468-x
更新日期:2014-10-01 00:00:00
abstract::This commentary serves as an introduction to the magnetic resonance imaging (MRI) technique called diffusion kurtosis imaging (DKI) employed in the study by Arab et al. in the present issue of Neurotoxicology Research. In their study, DKI is employed for longitudinal investigation of a methamphetamine intoxication mod...
journal_title:Neurotoxicity research
pub_type: 评论,杂志文章
doi:10.1007/s12640-019-00100-3
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abstract::The original version of this article contained mistakes, and the authors would like to correct them. Some parts of the image in Figure 5 were missing. The correct Figure 5 is shown at the next page. ...
journal_title:Neurotoxicity research
pub_type: 已发布勘误
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journal_title:Neurotoxicity research
pub_type: 杂志文章,评审
doi:10.1007/BF03033386
更新日期:2003-01-01 00:00:00
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journal_title:Neurotoxicity research
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doi:10.1007/s12640-015-9556-6
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journal_title:Neurotoxicity research
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journal_title:Neurotoxicity research
pub_type: 杂志文章
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journal_title:Neurotoxicity research
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更新日期:2015-07-01 00:00:00
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journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/s12640-019-00044-8
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journal_title:Neurotoxicity research
pub_type: 杂志文章
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journal_title:Neurotoxicity research
pub_type: 杂志文章
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更新日期:2004-01-01 00:00:00
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journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/s12640-020-00231-y
更新日期:2020-08-01 00:00:00
abstract::The mitochondrial toxin, 3-nitropropionic acid (3-NP), produces motor dysfunction and striatal atrophy in rats. However, rat strain and method of administration may contribute to variability in the deficits caused by 3-NP toxicity. To evaluate this, changes in nocturnal spontaneous locomotor activity from chronic admi...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/BF03033979
更新日期:2005-11-01 00:00:00
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journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1080/1029842021000022089
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journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/BF03033901
更新日期:2007-07-01 00:00:00
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journal_title:Neurotoxicity research
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doi:10.1007/s12640-019-0007-7
更新日期:2019-04-01 00:00:00
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journal_title:Neurotoxicity research
pub_type: 杂志文章,评审
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journal_title:Neurotoxicity research
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journal_title:Neurotoxicity research
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journal_title:Neurotoxicity research
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journal_title:Neurotoxicity research
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journal_title:Neurotoxicity research
pub_type: 杂志文章
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journal_title:Neurotoxicity research
pub_type: 杂志文章,评审
doi:10.1007/BF03033804
更新日期:2008-10-01 00:00:00
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journal_title:Neurotoxicity research
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doi:10.1007/s12640-011-9250-2
更新日期:2011-11-01 00:00:00
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journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/s12640-014-9500-1
更新日期:2015-04-01 00:00:00
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journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/s12640-018-9874-6
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journal_title:Neurotoxicity research
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journal_title:Neurotoxicity research
pub_type: 杂志文章
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更新日期:2019-04-01 00:00:00
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journal_title:Neurotoxicity research
pub_type: 杂志文章
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