Propranolol Modulates Cerebellar Circuit Activity and Reduces Tremor.

Authors

Joy Zhou
Meike E Van der Heijden
Luis E Salazar Leon
Tao Lin
Lauren N Miterko
Dominic J Kizek
Ross M Perez
Matea Pavešković
Amanda M Brown
Roy V Sillitoe

Language

English

Publication Date

12-1-2022

Journal

Cells

DOI

10.3390/cells11233889

PMID

36497147

PMCID

PMC9740691

PubMedCentral® Posted Date

12-1-2022

PubMedCentral® Full Text Version

Post-print

Abstract

Tremor is the most common movement disorder. Several drugs reduce tremor severity, but no cures are available. Propranolol, a β-adrenergic receptor blocker, is the leading treatment for tremor. However, the in vivo circuit mechanisms by which propranolol decreases tremor remain unclear. Here, we test whether propranolol modulates activity in the cerebellum, a key node in the tremor network. We investigated the effects of propranolol in healthy control mice and Car8^wdl/wdl mice, which exhibit pathophysiological tremor and ataxia due to cerebellar dysfunction. Propranolol reduced physiological tremor in control mice and reduced pathophysiological tremor in Car8^wdl/wdl mice to control levels. Open field and footprinting assays showed that propranolol did not correct ataxia in Car8^wdl/wdl mice. In vivo recordings in awake mice revealed that propranolol modulates the spiking activity of control and Car8^wdl/wdl Purkinje cells. Recordings in cerebellar nuclei neurons, the targets of Purkinje cells, also revealed altered activity in propranolol-treated control and Car8^wdl/wdl mice. Next, we tested whether propranolol reduces tremor through β1 and β2 adrenergic receptors. Propranolol did not change tremor amplitude or cerebellar nuclei activity in β1 and β2 null mice or Car8^wdl/wdl mice lacking β1 and β2 receptor function. These data show that propranolol can modulate cerebellar circuit activity through β-adrenergic receptors and may contribute to tremor therapeutics.

Keywords

Mice, Animals, Propranolol, Cerebellum, Purkinje Cells, Ataxia, Neurons, Adrenergic beta-Antagonists, Mice, Knockout, Nerve Tissue Proteins, Biomarkers, Tumor, cerebellum, tremor, propranolol, circuitry, beta-adrenergic receptors, electrophysiology

Published Open-Access

yes

Recommended Citation

Zhou, Joy; Van der Heijden, Meike E; Salazar Leon, Luis E; et al., "Propranolol Modulates Cerebellar Circuit Activity and Reduces Tremor." (2022). Duncan NRI Faculty and Staff Publications. 96.
https://digitalcommons.library.tmc.edu/duncar_nri_pub/96