| First Author | van den Maagdenberg AM | Year | 2004 |
| Journal | Neuron | Volume | 41 |
| Issue | 5 | Pages | 701-10 |
| PubMed ID | 15003170 | Mgi Jnum | J:88693 |
| Mgi Id | MGI:3036928 | Doi | 10.1016/s0896-6273(04)00085-6 |
| Citation | van den Maagdenberg AM, et al. (2004) A Cacna1a knockin migraine mouse model with increased susceptibility to cortical spreading depression. Neuron 41(5):701-10 |
| abstractText | 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. |
