Conditional ablation of brain-derived neurotrophic factor-TrkB signaling impairs striatal neuron development

Yun Li, Daishi Yui, Bryan W. Luikart, Renée M. McKay, Yanjiao Li, John L. Rubenstein, Luis F. Parada

Research output: Contribution to journalArticlepeer-review

44 Scopus citations

Abstract

Neurotrophic factors, such as brain-derived neurotrophic factor (BDNF), are associated with the physiology of the striatum and the loss of its normal functioning under pathological conditions. The role of BDNF and its downstream signaling in regulating the development of the striatum has not been fully investigated, however. Here we report that ablation of Bdnf in both the cortex and substantia nigra depletes BDNF in the striatum, and leads to impaired striatal development, severe motor deficits, and postnatal lethality. Furthermore, striatal-specific ablation of TrkB, the gene encoding the high-affinity receptor for BDNF, is sufficient to elicit an array of striatal developmental abnormalities, including decreased anatomical volume, smaller neuronal nucleus size, loss of dendritic spines, reduced enkephalin expression, diminished nigral dopaminergic projections, and severe deficits in striatal dopamine signaling through DARPP32. In addition, TrkB ablation in striatal neurons elicits a non-cell-autonomous reduction of tyrosine hydroxylase protein level in the axonal projections of substantia nigral dopaminergic neurons. Thus, our results establish an essential function for TrkB in regulating the development of striatal neurons.

Original languageEnglish (US)
Pages (from-to)15491-15496
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume109
Issue number38
DOIs
StatePublished - Sep 18 2012

Keywords

  • Huntington disease
  • Neurotrophin

ASJC Scopus subject areas

  • General

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