RT Journal Article
SR Electronic
T1 Age-Dependent Maintenance of Motor Controland Corticostriatal Innervation by Death Receptor 3
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 3782
OP 3792
DO 10.1523/JNEUROSCI.1928-09.2010
VO 30
IS 10
A1 Jason Peter Twohig
A1 Malcolm I. Roberts
A1 Nuria Gavalda
A1 Emma L. Rees-Taylor
A1 Albert Giralt
A1 Debbie Adams
A1 Simon P. Brooks
A1 Melanie J. Bull
A1 Claudia J. Calder
A1 Simone Cuff
A1 Audrey A. Yong
A1 Jordi Alberch
A1 Alun Davies
A1 Stephen B. Dunnett
A1 Aviva M. Tolkovsky
A1 Eddie C. Y. Wang
YR 2010
UL http://www.jneurosci.org/content/30/10/3782.abstract
AB 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.