Publication Type Academic Article
Authors Plotkin J, Day M, Peterson J, Xie Z, Kress G, Rafalovich I, Kondapalli J, Gertler T, Flajolet M, Greengard P, Stavarache M, Kaplitt M, Rosinski J, Chan C, Surmeier D
Journal Neuron
Volume 83
Issue 1
Pagination 178-88
Date Published 07/02/2014
ISSN 1097-4199
Keywords Cerebral Cortex, Corpus Striatum, Disease Models, Animal, Huntington Disease, Receptor, trkB, Signal Transduction
Abstract Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder. The debilitating choreic movements that plague HD patients have been attributed to striatal degeneration induced by the loss of cortically supplied brain-derived neurotrophic factor (BDNF). Here, we show that in mouse models of early symptomatic HD, BDNF delivery to the striatum and its activation of tyrosine-related kinase B (TrkB) receptors were normal. However, in striatal neurons responsible for movement suppression, TrkB receptors failed to properly engage postsynaptic signaling mechanisms controlling the induction of potentiation at corticostriatal synapses. Plasticity was rescued by inhibiting p75 neurotrophin receptor (p75NTR) signaling or its downstream target phosphatase-and-tensin-homolog-deleted-on-chromosome-10 (PTEN). Thus, corticostriatal synaptic dysfunction early in HD is attributable to a correctable defect in the response to BDNF, not its delivery.
DOI 10.1016/j.neuron.2014.05.032
PubMed ID 24991961
PubMed Central ID PMC4131293
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