Objective: The aim of this work was to study the effect of harmaline-induced tremor on cortical oscillatory activities, and the sensitivity of potential EEG signatures to the reference drugs.

Background: Essential tremor (ET) is a one of the most common form of movement disorders, which is characterized by the apparition of postural tremor and intensifies when one tries to use the affected muscles. ET typically involves a tremor of the arms, hands or fingers. Several treatment options are available depending on the severity of the disease. The first line medication is beta-blockers such as propranolol or the anti-epileptic primidone. Second line medications are the anti-epileptics topiramate, gabapentin and levetiracetam given as an add-on therapy with the first line drug. Despite the wide possibility of medications a large number of patients are not adequately relieved. There is therefore an urgent need to find new specific treatments for ET. The most widely used animal model of essential tremor is generated by the administration of the beta-carbolin (harmaline) in mice. Harmaline induces long-lasting tremors in mice by increasing neuronal synchrony and rhythmicity in the olivocerebellar system. In this model the classical read-out is the recording of tremor frequency that occurs between 8 to 10Hz.

Methods: In this study we recorded cortical EEG activities in mice after the injection of harmaline.

Results: We found that harmaline (10, 20, 30mg/kg) dose-dependently increased the power of cortical oscillations in the 15-60Hz range, along with action tremors. This power increase appeared within a few minutes after treatment and remained stable for at least 2h30. This oscillation was also present, to a lesser extent, in other brain structures, such as the hippocampus. A 20 minutes pre-treatment with the first-line medication propranolol (10mg/kg) strongly attenuated the harmaline-induced tremors and reversed the 35-60Hz oscillation to control levels.

Conclusions: These electrophysiological signatures of the rodent harmaline model might constitute a powerful tool for drug development for essential tremor.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/identification-of-a-new-biomarker-in-a-mouse-model-of-essential-tremor-using-eeg/