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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
10
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pubmed:dateCreated |
2004-11-19
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pubmed:abstractText |
Mutations of Presenilin-1 are the major cause of familial Alzheimer's disease. Presenilin-1 knockout (PS1-/-) mice develop severe cortical dysplasia related to human type 2 lissencephaly. This overmigration syndrome has been attributed to the premature loss of Cajal-Retzius cells (CRcs), pioneer neurons required for the termination of radial neuronal migration. To elucidate the potential cellular mechanisms responsible for this premature neuronal loss, we investigated the morphological and electrophysiological properties of visually identified CRcs of wild-type (WT) and PS1-/- mouse brains at embryonic day 16.5. The density of CRcs was substantially reduced in the cerebral cortex of PS1-/-. In PS1-/- CRcs the number of axonal branches was significantly increased to 12.5 +/- 4.9 (n = 8; WT, 4.0 +/- 1.4, n = 12), while no differences in dendritic branching and total length of dendritic and axonal compartments were observed. Additionally, the resting membrane potential of PS1-/- CRcs was significantly depolarized (-48.3 +/- 1.7 mV; n = 23) in contrast to WT CRcs (-57.9 +/- 2.1 mV; n = 38). Active membrane properties were not affected by PS1 deficiency. CRcs of both genotypes showed spontaneous postsynaptic currents that could be completely blocked by 100 microM bicuculline and were unaffected by glutamatergic antagonists, suggesting that they were mediated by GABAA receptors. These results demonstrate that axonal branching and resting membrane potential of CRcs was affected in embryonic cerebral cortex of PS1-/- mice. The depolarized membrane potential observed in PS1-/- CRcs may increase the susceptibility to neuronal death, thus facilitating the premature loss of CRcs in PS1-/- mice.
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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/2-Amino-5-phosphonovalerate,
http://linkedlifedata.com/resource/pubmed/chemical/6-Cyano-7-nitroquinoxaline-2,3-dione,
http://linkedlifedata.com/resource/pubmed/chemical/Bicuculline,
http://linkedlifedata.com/resource/pubmed/chemical/Cell Adhesion Molecules, Neuronal,
http://linkedlifedata.com/resource/pubmed/chemical/Excitatory Amino Acid Agonists,
http://linkedlifedata.com/resource/pubmed/chemical/Excitatory Amino Acid Antagonists,
http://linkedlifedata.com/resource/pubmed/chemical/Extracellular Matrix Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/GABA Antagonists,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Nerve Tissue Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/PSEN1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Presenilin-1,
http://linkedlifedata.com/resource/pubmed/chemical/Serine Endopeptidases,
http://linkedlifedata.com/resource/pubmed/chemical/reelin protein
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0953-816X
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
20
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2749-56
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:15548218-2-Amino-5-phosphonovalerate,
pubmed-meshheading:15548218-6-Cyano-7-nitroquinoxaline-2,3-dione,
pubmed-meshheading:15548218-Animals,
pubmed-meshheading:15548218-Bicuculline,
pubmed-meshheading:15548218-Cell Adhesion Molecules, Neuronal,
pubmed-meshheading:15548218-Cerebral Cortex,
pubmed-meshheading:15548218-Electric Stimulation,
pubmed-meshheading:15548218-Embryo, Mammalian,
pubmed-meshheading:15548218-Excitatory Amino Acid Agonists,
pubmed-meshheading:15548218-Excitatory Amino Acid Antagonists,
pubmed-meshheading:15548218-Excitatory Postsynaptic Potentials,
pubmed-meshheading:15548218-Extracellular Matrix Proteins,
pubmed-meshheading:15548218-GABA Antagonists,
pubmed-meshheading:15548218-Immunohistochemistry,
pubmed-meshheading:15548218-Membrane Potentials,
pubmed-meshheading:15548218-Membrane Proteins,
pubmed-meshheading:15548218-Mice,
pubmed-meshheading:15548218-Mice, Knockout,
pubmed-meshheading:15548218-Nerve Tissue Proteins,
pubmed-meshheading:15548218-Neurons,
pubmed-meshheading:15548218-Presenilin-1,
pubmed-meshheading:15548218-Serine Endopeptidases,
pubmed-meshheading:15548218-Stem Cells
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pubmed:year |
2004
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pubmed:articleTitle |
Altered morphological and electrophysiological properties of Cajal-Retzius cells in cerebral cortex of embryonic Presenilin-1 knockout mice.
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pubmed:affiliation |
Institute of Physiology and Pathophysiology, University of Mainz, Duesbergweg 6, D-55099 Mainz, Germany. wkilb@uni-mainz.de
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, Non-U.S. Gov't
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