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Age-dependent maintenance of motor controland corticostriatal innervation by death receptor 3

Twohig, Jason Peter, Roberts, Malcolm I., Gavalda, Nuria, Rees-Taylor, Emma Louise, Giralt, Albert, Adams, Deborah, Brooks, Simon Philip, Bull, Melanie Jane, Calder, Claudia Jane, Cuff, Simone, Yong, Audrey Alice, Alberch, Jordi, Davies, Alun M., Dunnett, Stephen Bruce, Tolkovsky, Aviva M. and Wang, Edward Chung Yern 2010. Age-dependent maintenance of motor controland corticostriatal innervation by death receptor 3. Journal of Neuroscience 30 (10) , pp. 3782-3792. 10.1523/JNEUROSCI.1928-09.2010

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Abstract

Death receptor 3 is a proinflammatory member of the immunomodulatory tumor necrosis factor receptor superfamily, which has been implicated in several inflammatory diseases such as arthritis and inflammatory bowel disease. Intriguingly however, constitutive DR3 expression has been detected in the brains of mice, rats, and humans, although its neurological function remains unknown. By mapping the normal brain expression pattern of DR3, we found that DR3 is expressed specifically by cells of the neuron lineage in a developmentally regulated and region-specific pattern. Behavioral studies on DR3-deficient (DR3ko) mice showed that constitutive neuronal DR3 expression was required for stable motor control function in the aging adult. DR3ko mice progressively developed behavioral defects characterized by altered gait, dyskinesia, and hyperactivity, which were associated with elevated dopamine and lower serotonin levels in the striatum. Importantly, retrograde tracing showed that absence of DR3 expression led to the loss of corticostriatal innervation without significant neuronal loss in aged DR3ko mice. These studies indicate that DR3 plays a key nonredundant role in the retention of normal motor control function during aging in mice and implicate DR3 in progressive neurological disease.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Medicine
Systems Immunity Research Institute (SIURI)
Subjects: R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Additional Information: Pdf uploaded in accordance with publisher's policy at http://www.jneurosci.org/site/misc/ifa_policies.xhtml#copyright (accessed 26/02/2014).
Publisher: Society for Neuroscience
ISSN: 0270-6474
Date of First Compliant Deposit: 30 March 2016
Last Modified: 03 Jun 2019 19:15
URI: http://orca.cf.ac.uk/id/eprint/8787

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