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Neuron. 2004 Mar 4;41(5):701-10.

A Cacna1a knockin migraine mouse model with increased susceptibility to cortical spreading depression.

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1
Department of Biomedical Sciences, University of Padova, CNR Institute of Neuroscience, Viale G. Colombo 3, 35121 Padova, Italy. dani@civ.bio.unipd.it

Abstract

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.

PMID:
15003170
DOI:
10.1016/s0896-6273(04)00085-6
[Indexed for MEDLINE]
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