Regulation of motor function and behavior by atypical chemokine receptor 1.
Publication/Presentation Date
9-1-2014
Abstract
Atypical Chemokine Receptor 1 (ACKR1), previously known as Duffy Antigen Receptor for Chemokines, stands out among chemokine receptors for high selective expression on cerebellar Purkinje neurons. Although ACKR1 ligands activate Purkinje cells in vitro, evidence for ACKR1 regulation of brain function in vivo is lacking. Here we demonstrate that Ackr1 (-/-) mice have markedly impaired balance and ataxia on a rotating rod and increased tremor when injected with harmaline, which induces whole-body tremor by activating Purkinje cells. Ackr1 (-/-) mice also exhibited impaired exploratory behavior, increased anxiety-like behavior and frequent episodes of marked hypoactivity under low-stress conditions. Surprisingly, Ackr1 (+/-) had similar behavioral abnormalities, indicating pronounced haploinsufficiency. The behavioral phenotype of Ackr1 (-/-) mice was the opposite of mouse models of cerebellar degeneration, and the defects persisted when Ackr1 was deficient only on non-hematopoietic cells. Together, the results suggest that normal motor function and behavior may partly depend on negative regulation of Purkinje cell activity by Ackr1.
Volume
44
Issue
5
First Page
498
Last Page
515
ISSN
1573-3297
Published In/Presented At
Schneider, E. H., Fowler, S. C., Lionakis, M. S., Swamydas, M., Holmes, G., Diaz, V., Munasinghe, J., Peiper, S. C., Gao, J. L., & Murphy, P. M. (2014). Regulation of motor function and behavior by atypical chemokine receptor 1. Behavior genetics, 44(5), 498–515. https://doi.org/10.1007/s10519-014-9665-7
Disciplines
Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods
PubMedID
24997773
Department(s)
Administration and Leadership
Document Type
Article