Caroline ROUAUX (Université de Strasbourg) – Cortical hyperexcitability in amyotrophic lateral sclerosis : new means and new players

Description

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease, characterized by the death of upper (UMN) and lower motor neurons (LMN). A unifying feature of both sporadic and familial forms of ALS is cortical hyperexcitability, which precedes symptom onset, negatively correlates with survival, and is sufficient to trigger UMN and LMN degeneration in rodents. Using electrocorticography in ALS mouse models, and standard EEG recordings in sporadic ALS patients, we demonstrate that cortical dysfunction in ALS also manifests by a deficit in theta-gamma phase-amplitude-coupling (PAC), which correlates with disease progression. Mechanistically, we unravel a selective reduction of noradrenaline (NA) both in patients and animals, that critically contribute to cortical hyperexcitability, paving the way for hitherto non-explored therapeutic strategies.

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