Modulation of GABAergic dysfunction due to SCN1A mutation linked to Hippocampal Sclerosis
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Ruffolo G., Martinello K., Labate A., Cifelli P., Fucile S., Di Gennaro G., Quattrone A., Esposito V., Limatola C., Giangaspero F., Aronica E., Palma E., Gambardella A.
DOI: 10.1002/acn3.51150
ISSN: 2328-9503
We compared GABAergic function and neuronal excitability in the hippocampal tissue of seven sporadic MTLE patients with a patient carrying a SCN1A loss-of-function mutation. All had excellent outcome from anterior temporal lobectomy, and neuropathological study always showed characteristic hippocampal sclerosis (Hs). Compared to MTLE patients, there was a more severe impairment of GABAergic transmission, due to the lower GABAergic activity related to the NaV1.1 loss-of-function, in addition to the typical GABA-current rundown, a hallmark of sporadic MTLE. Our results give evidence that a pharmacological rescuing of the GABAergic dysfunction may represent a promising strategy for the treatment of these patients.