First FHM3 mouse model shows spontaneous cortical spreading depolarizations

Area of Science:

• Neuroscience
• Genetics
• Neurology

Background:

• Migraine with aura is a debilitating neurological condition.
• Cortical spreading depolarization (CSD) is the electrophysiological phenomenon underlying migraine aura.
• Familial hemiplegic migraine type 3 (FHM3) is a rare, severe form of migraine with aura.

Purpose of the Study:

• To establish and characterize the first transgenic mouse model for familial hemiplegic migraine type 3 (FHM3).
• To investigate the occurrence and propagation of spontaneous cortical spreading depolarization (CSD) events in this novel FHM3 model.
• To provide a preclinical tool for studying the mechanisms of migraine with aura.

Main Methods:

• Generation of a transgenic mouse model expressing L263V-mutated α1 subunits in voltage-gated Na_V 1.1 sodium channels (Scn1a^L263V).
• Electrophysiological recording to detect and analyze spontaneous cortical spreading depolarization (CSD) events.
• Observation of CSD propagation patterns within the cortex.

Main Results:

• Spontaneous cortical spreading depolarization (CSD) events were observed for the first time in this FHM3 mouse model.
• CSDs consistently propagated from the visual cortex to the motor cortex.
• The observed CSD patterns in the mouse model recapitulated those seen in human patients with migraine with aura.

Conclusions:

• The developed FHM3 transgenic mouse model successfully exhibits spontaneous CSD events.
• This model serves as a valuable tool for preclinical research into migraine with aura.
• The model may also be applicable to studying other diseases characterized by spreading depolarization.