| A Cacna1a knockin migraine mouse model with increased susceptibility to cortical spreading depression. | |
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MedLine Citation:
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PMID: 15003170 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Migraine is a common, disabling, multifactorial, episodic neurovascular disorder of unknown etiology. Familial hemiplegic migraine type 1 (FHM-1) is a Mendelian subtype of migraine with aura that is caused by missense mutations in the CACNA1A gene that encodes the alpha(1) subunit of neuronal Ca(v)2.1 Ca(2+) channels. We generated a knockin mouse model carrying the human pure FHM-1 R192Q mutation and found multiple gain-of-function effects. These include increased Ca(v)2.1 current density in cerebellar neurons, enhanced neurotransmission at the neuromuscular junction, and, in the intact animal, a reduced threshold and increased velocity of cortical spreading depression (CSD; the likely mechanism for the migraine aura). Our data show that the increased susceptibility for CSD and aura in migraine may be due to cortical hyperexcitability. The R192Q FHM-1 mouse is a promising animal model to study migraine mechanisms and treatments. |
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Authors:
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Arn M J M van den Maagdenberg; Daniela Pietrobon; Tommaso Pizzorusso; Simon Kaja; Ludo A M Broos; Tiziana Cesetti; Rob C G van de Ven; Angelita Tottene; Jos van der Kaa; Jaap J Plomp; Rune R Frants; Michel D Ferrari |
Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Neuron Volume: 41 ISSN: 0896-6273 ISO Abbreviation: Neuron Publication Date: 2004 Mar |
Date Detail:
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Created Date: 2004-03-08 Completed Date: 2004-04-12 Revised Date: 2012-02-22 |
Medline Journal Info:
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Nlm Unique ID: 8809320 Medline TA: Neuron Country: United States |
Other Details:
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Languages: eng Pagination: 701-10 Citation Subset: IM |
Affiliation:
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Department of Biomedical Sciences, University of Padova, CNR Institute of Neuroscience, Viale G. Colombo 3, 35121 Padova, Italy. dani@civ.bio.unipd.it |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Calcium Channels / biosynthesis, genetics* Calcium Channels, P-Type Calcium Channels, Q-Type Cells, Cultured Cortical Spreading Depression / genetics* Disease Models, Animal* Female Genetic Predisposition to Disease* Humans Male Mice Mice, Mutant Strains Mice, Transgenic Migraine with Aura / genetics*, metabolism Motor Endplate / genetics, metabolism Mutation Recombination, Genetic* |
| Grant Support | |
ID/Acronym/Agency:
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E.0847//Telethon; E.1297//Telethon |
| Chemical | |
Reg. No./Substance:
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0/CACNA1A protein, human; 0/Cacna1a protein, mouse; 0/Calcium Channels; 0/Calcium Channels, P-Type; 0/Calcium Channels, Q-Type |
| Comments/Corrections | |
Comment In:
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Neuron. 2004 Mar 4;41(5):679-80
[PMID:
15003166
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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