Impaired TrkB Receptor Signaling Underlies Corticostriatal Dysfunction in Huntington’s Disease
| Autor: | D. James Surmeier, C. Savio Chan, Jayms D. Peterson, Michael G. Kaplitt, Geraldine J. Kress, Zhong Xie, Mihaela Stavarache, Marc Flajolet, Jim Rosinski, Joshua L. Plotkin, Tracy S. Gertler, Michelle Day, Jyothisri Kondapalli, Igor Rafalovich, Paul Greengard |
|---|---|
| Jazyk: | angličtina |
| Předmět: |
medicine.medical_specialty
Choreiform movement Neuroscience(all) Mice Transgenic Striatum Tropomyosin receptor kinase B Biology Article Mice Organ Culture Techniques Huntington's disease Neurotrophic factors Internal medicine medicine Low-affinity nerve growth factor receptor Animals Receptor trkB Gene Knock-In Techniques Cerebral Cortex General Neuroscience Long-term potentiation medicine.disease Corpus Striatum Mice Inbred C57BL Disease Models Animal Endocrinology Huntington Disease nervous system Signal transduction Neuroscience Signal Transduction |
| Zdroj: | Neuron. (1):178-188 |
| ISSN: | 0896-6273 |
| DOI: | 10.1016/j.neuron.2014.05.032 |
| Popis: | SUMMARY 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-deletedon-chromosome-10 (PTEN). Thus, corticostriatal synaptic dysfunction early in HD is attributable to a correctable defect in the response to BDNF, not its delivery. |
| Databáze: | OpenAIRE |
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