RT Journal Article
SR Electronic
T1 Abnormal Dysbindin Expression in Cerebellar Mossy Fiber Synapses in the mdx Mouse Model of Duchenne Muscular Dystrophy
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 6576
OP 6585
DO 10.1523/JNEUROSCI.23-16-06576.2003
VO 23
IS 16
A1 Roy V. Sillitoe
A1 Matthew A. Benson
A1 Derek J. Blake
A1 Richard Hawkes
YR 2003
UL http://www.jneurosci.org/content/23/16/6576.abstract
AB The dystrophin-associated protein complex (DPC), comprising sarcoglycans, dystroglycans, dystrobrevins, and syntrophins, is a component of synapses both in muscle and brain. Dysbindin is a novel component of the DPC, which binds to β-dystrobrevin and may serve as an adaptor protein that links the DPC to an intracellular signaling cascade. Disruption of the DPC results in muscular dystrophy, and mutations in the human ortholog of dysbindin have been implicated in the pathogenesis of schizophrenia. In both cases, patients also present with neurological symptoms reminiscent of cerebellar problems. In the mouse cerebellum, dysbindin immunoreactivity is expressed at high levels in a subset of mossy fiber synaptic glomeruli in the granular layer. Lower levels of dysbindin immunoreactivity are also detected in Purkinje cell dendrites. In the cerebellar vermis, dysbindin-immunoreactive glomeruli are restricted to an array of parasagittal stripes that bears a consistent relationship to Purkinje cell parasagittal band boundaries as defined by the expression of the respiratory isoenzyme zebrin II/aldolase c. In a mouse model of Duchenne muscular dystrophy, the mdx mutant, in which dystrophin is not expressed, there is a dramatic increase in the number of dysbindin-immunoreactive glomeruli in the posterior cerebellar vermis. Moreover, the topography of the terminal fields is disrupted, replacing the stripes by a homogeneous distribution. Abnormal synaptic organization in the cerebellum may contribute to the neurological problems associated with muscular dystrophy and schizophrenia.