Regulation of Motor Function and Behavior by Atypical Chemokine Receptor 1

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Issue Date
2014-09Author
Schneider, Erich H.
Fowler, Stephen C.
Lionakis, Michail S.
Swamydas, Muthulekha
Holmes, Gibran
Diaz, Vivian
Munasinghe, Jeeva
Peiper, Stephen C.
Gao, Ji-Liang
Murphy, Philip M.
Publisher
Springer Verlag
Type
Article
Article Version
Scholarly/refereed, author accepted manuscript
Rights
© Springer Science+Business Media New York (outside the USA) 2014
Metadata
Show full item recordAbstract
Atypical Chemokine Receptor 1 (ACKR1), previously known as the Duffy Antigen Receptor for Chemokines, stands out among chemokine receptors for its high selective expression on Purkinje cells of the cerebellum, consistent with the ability of ACKR1 ligands to activate Purkinje cells in vitro. Nevertheless, evidence for ACKR1 regulation of brain function in vivo has been lacking. Here we demonstrate that Ackr1−/− mice have markedly impaired balance and ataxia when placed on a rotating rod and increased tremor when injected with harmaline, a drug that 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. The behavioral phenotype of Ackr1−/− mice was the opposite of the phenotype occurring in mice with cerebellar degeneration and the defects persisted when Ackr1 was deficient only on non-hematopoietic cells. We conclude that normal motor function and behavior depend in part on negative regulation of Purkinje cell activity by Ackr1.
Description
The final publication is available at Springer via http://dx.doi.org/10.1007/s10519-014-9665-7
Collections
- Pharmacy Scholarly Works [293]
Citation
Schneider, E. H., Fowler, S. C., Lionakis, M. S., Swamydas, M., Holmes, G., Diaz, V., … Murphy, P. M. (2014). Regulation of Motor Function and Behavior by Atypical Chemokine Receptor 1. Behavior Genetics, 44(5), 498–515. http://doi.org/10.1007/s10519-014-9665-7
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