Modulation of GABAergic dysfunction due to SCN1A mutation linked to Hippocampal Sclerosis

Gabriele Ruffolo; Katiuscia Martinello; Angelo Labate; Pierangelo Cifelli; Sergio Fucile; Giancarlo Di Gennaro; Andrea Quattrone; Vincenzo Esposito; Cristina Limatola; Felice Giangaspero; Eleonora Aronica; Eleonora Palma; Antonio Gambardella

doi:10.1002/acn3.51150

Modulation of GABAergic dysfunction due to SCN1A mutation linked to Hippocampal Sclerosis

Gabriele Ruffolo, Katiuscia Martinello, Angelo Labate, Pierangelo Cifelli, Sergio Fucile, Giancarlo Di Gennaro, Andrea Quattrone, Vincenzo Esposito, Cristina Limatola, Felice Giangaspero, Eleonora Aronica, Eleonora Palma, Antonio Gambardella

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Abstract

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 NaV 1.1 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.

Original language	English
Journal	Annals of Clinical and Translational Neurology
DOIs	https://doi.org/10.1002/acn3.51150
Publication status	E-pub ahead of print - Aug 5 2020

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Modulation of GABAergicFinal published version, 847 KB

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Modulation of GABAergic dysfunction due to SCN1A mutation linked to Hippocampal Sclerosis. / Ruffolo, Gabriele; Martinello, Katiuscia; Labate, Angelo; Cifelli, Pierangelo; Fucile, Sergio ; Di Gennaro, Giancarlo; Quattrone, Andrea; Esposito, Vincenzo ; Limatola, Cristina ; Giangaspero, Felice; Aronica, Eleonora; Palma, Eleonora; Gambardella, Antonio.

In: Annals of Clinical and Translational Neurology, 05.08.2020.

Research output: Contribution to journal › Article › peer-review

Ruffolo, Gabriele ; Martinello, Katiuscia ; Labate, Angelo ; Cifelli, Pierangelo ; Fucile, Sergio ; Di Gennaro, Giancarlo ; Quattrone, Andrea ; Esposito, Vincenzo ; Limatola, Cristina ; Giangaspero, Felice ; Aronica, Eleonora ; Palma, Eleonora ; Gambardella, Antonio. / Modulation of GABAergic dysfunction due to SCN1A mutation linked to Hippocampal Sclerosis. In: Annals of Clinical and Translational Neurology. 2020.

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abstract = "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 NaV 1.1 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.",

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AU - Cifelli, Pierangelo

AU - Fucile, Sergio

AU - Di Gennaro, Giancarlo

AU - Quattrone, Andrea

AU - Esposito, Vincenzo

AU - Limatola, Cristina

AU - Giangaspero, Felice

AU - Aronica, Eleonora

AU - Palma, Eleonora

AU - Gambardella, Antonio

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Modulation of GABAergic dysfunction due to SCN1A mutation linked to Hippocampal Sclerosis

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