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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
2004-6-14
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pubmed:abstractText |
The developing rodent brain is vulnerable to pharmacological blockade of N-methyl-d-aspartate (NMDA) receptors which can lead to severe and disseminated apoptotic neurodegeneration. Here, we show that systemic administration of the NMDA receptor antagonist MK801 to 7-day-old rats leads to impaired activity of extracellular signal-regulated kinase 1/2 (ERK1/2) and reduces levels of phosphorylated cAMP-responsive element binding protein (CREB) in brain regions which display severe apoptotic neurodegeneration. Impaired ERK1/2 and CREB activity were temporally paralleled by sustained depletion of neurotrophin expression, particularly brain-derived neurotrophic factor (BDNF). BDNF supplementation fully prevented MK801-induced neurotoxicity in immature neuronal cultures and transgenic constitutive activation of Ras was associated with marked protection against MK801-induced apoptotic neuronal death. These data indicate that uncoupling of NMDA receptors from the ERK1/2-CREB signaling pathway in vivo results in massive apoptotic deletion of neurons in the developing rodent brain.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP Response...,
http://linkedlifedata.com/resource/pubmed/chemical/Dizocilpine Maleate,
http://linkedlifedata.com/resource/pubmed/chemical/Excitatory Amino Acid Antagonists,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 1,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Nerve Growth Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-bcl-2,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, N-Methyl-D-Aspartate,
http://linkedlifedata.com/resource/pubmed/chemical/ras Proteins
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0969-9961
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pubmed:author |
pubmed-author:BittigauPetraP,
pubmed-author:BriemTimT,
pubmed-author:DzietkoMarkM,
pubmed-author:HansenHenrik HHH,
pubmed-author:HeumannRolfR,
pubmed-author:IkonomidouChrysanthyC,
pubmed-author:RzeskiWojciechW,
pubmed-author:SifringerMarcoM,
pubmed-author:StepulakAndrzejA,
pubmed-author:ThorFriederikeF,
pubmed-author:VossAlexanderA,
pubmed-author:ZdzisinskaBarbaraB
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pubmed:issnType |
Print
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pubmed:volume |
16
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
440-53
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:15193300-Age Factors,
pubmed-meshheading:15193300-Animals,
pubmed-meshheading:15193300-Apoptosis,
pubmed-meshheading:15193300-Cells, Cultured,
pubmed-meshheading:15193300-Cyclic AMP Response Element-Binding Protein,
pubmed-meshheading:15193300-Dizocilpine Maleate,
pubmed-meshheading:15193300-Down-Regulation,
pubmed-meshheading:15193300-Excitatory Amino Acid Antagonists,
pubmed-meshheading:15193300-Gene Expression,
pubmed-meshheading:15193300-Gyrus Cinguli,
pubmed-meshheading:15193300-MAP Kinase Signaling System,
pubmed-meshheading:15193300-Mitogen-Activated Protein Kinase 1,
pubmed-meshheading:15193300-Mitogen-Activated Protein Kinase 3,
pubmed-meshheading:15193300-Mitogen-Activated Protein Kinases,
pubmed-meshheading:15193300-Nerve Degeneration,
pubmed-meshheading:15193300-Nerve Growth Factors,
pubmed-meshheading:15193300-Neurons,
pubmed-meshheading:15193300-Proto-Oncogene Proteins c-bcl-2,
pubmed-meshheading:15193300-RNA, Messenger,
pubmed-meshheading:15193300-Rats,
pubmed-meshheading:15193300-Rats, Wistar,
pubmed-meshheading:15193300-Receptors, N-Methyl-D-Aspartate,
pubmed-meshheading:15193300-Transcription, Genetic,
pubmed-meshheading:15193300-ras Proteins
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pubmed:year |
2004
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pubmed:articleTitle |
Mechanisms leading to disseminated apoptosis following NMDA receptor blockade in the developing rat brain.
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pubmed:affiliation |
Department of Pediatric Neurology,Campus Virchow Klinikum, and Neuroscience Research Center, Charité, Humboldt University, 10117, Berlin, Germany. henrik.hansen@charite.de
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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