Cerebellar α6GABA_A Receptors as a Therapeutic Target for Essential Tremor: Proof-of-Concept Study with Ethanol and Pyrazoloquinolinones.

ABSTRACT: Ethanol has been shown to suppress essential tremor (ET) in patients at low-to-moderate doses, but its mechanism(s) of action remain unknown. One of the ET hypotheses attributes the ET tremorgenesis to the over-activated firing of inferior olivary neurons, causing synchronic rhythmic firings of cerebellar Purkinje cells. Purkinje cells, however, also receive excitatory inputs from granule cells where the α6 subunit-containing GABA_A receptors (α6GABA_ARs) are abundantly expressed. Since ethanol is a positive allosteric modulator (PAM) of α6GABA_ARs, such action may mediate its anti-tremor effect. Employing the harmaline-induced ET model in male ICR mice, we evaluated the possible anti-tremor effects of ethanol and α6GABA_AR-selective pyrazoloquinolin

SUBMITTER: Huang YH 

PROVIDER: S-EPMC10121996 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature