Abstract:
:This study analyzes the electrophysiological cause and behavioral consequence of dopaminergic cell loss in a knockin mouse strain bearing hypersensitive nicotinic alpha4-receptor subunits ("L9'S mice"). Adult brains of L9'S mice show moderate loss of substantia nigra dopaminergic neurons and of striatal dopaminergic innervation. Amphetamine-stimulated locomotion is impaired, reflecting a reduction of dopamine stored in presynaptic vesicles. Recordings from dopaminergic neurons in L9'S mice show that 10 microM nicotine depolarizes cells and increases spiking rates in L9'S cells but hyperpolarizes and decreases spiking rates in wild-type (WT) cells. Thus dopaminergic neurons of L9'S mice have an excitatory response to nicotine which is qualitatively different from that of WT neurons. The cause of dopaminergic cell death is therefore probably an increased sensitivity to acetylcholine or choline of alpha4-containing nicotinic receptors. Hypersensitive excitatory stimulation during activation of alpha4-containing receptors provides the first evidence for cholinergic excitotoxicity as a cause of dopaminergic neuron death. This novel concept may be relevant to the pathophysiology of Parkinson disease.
journal_name
Physiol Genomicsjournal_title
Physiological genomicsauthors
Orb S,Wieacker J,Labarca C,Fonck C,Lester HA,Schwarz Jdoi
10.1152/physiolgenomics.00012.2004subject
Has Abstractpub_date
2004-08-11 00:00:00pages
299-307issue
3eissn
1094-8341issn
1531-2267pii
00012.2004journal_volume
18pub_type
杂志文章abstract::Megakaryocyte (MK) development is critically informed by plasma membrane-localized receptors that integrate a multiplicity of environmental cues. Given that the current understanding about receptors and ligands involved in megakaryocytopoiesis is based on single targets, we performed a genome-wide search to identify a...
journal_title:Physiological genomics
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journal_title:Physiological genomics
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doi:10.1152/physiolgenomics.00044.2001
更新日期:2001-10-10 00:00:00
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journal_title:Physiological genomics
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更新日期:2000-11-09 00:00:00
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journal_title:Physiological genomics
pub_type: 杂志文章,评审
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更新日期:2002-12-03 00:00:00
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journal_title:Physiological genomics
pub_type: 杂志文章
doi:10.1152/physiolgenomics.00044.2008
更新日期:2008-11-12 00:00:00
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journal_title:Physiological genomics
pub_type: 杂志文章
doi:10.1152/physiolgenomics.00030.2019
更新日期:2019-07-01 00:00:00
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journal_title:Physiological genomics
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doi:10.1152/physiolgenomics.00188.2003
更新日期:2004-03-12 00:00:00
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journal_title:Physiological genomics
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更新日期:2018-11-01 00:00:00
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journal_title:Physiological genomics
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journal_title:Physiological genomics
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journal_title:Physiological genomics
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journal_title:Physiological genomics
pub_type: 杂志文章
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journal_title:Physiological genomics
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journal_title:Physiological genomics
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