Long-term adeno-associated viral vector-mediated expression of truncated TrkB in the adult rat facial nucleus results in motor neuron degeneration.

Abstract

Adult facial motor neurons continue to express full-length TrkB tyrosine kinase receptor (TrkB.FL), the high-affinity receptor for the neurotrophins BDNF and neurotrophic factor-4/5 (NT-4/5), suggesting that they remain dependent on target-derived and locally produced neurotrophins in adulthood. Studies on the role of TrkB signaling in the adult CNS have been hampered by the early lethality of bdnf, nt-4/5, and trkB knock-out mice. We disrupted TrkB.FL signaling in adult facial motor neurons using adeno-associated viral vector-mediated overexpression of a naturally occurring dominant-negative TrkB receptor, TrkB.T1. Expression of TrkB.T1 resulted in neuronal atrophy and downregulation of NeuN (neuronal-specific nuclear protein) and ChAT expression in facial motor neurons. A subset of transduced neurons displayed signs of motor neuron degeneration that included dendritic beading and rounding of the soma at 2 months of TrkB.T1 expression. Cell counts revealed a significant reduction in motor neuron number in the facial nucleus at 4 months after onset of expression of TrkB.T1, suggesting that a proportion of TrkB.T1-expressing motor neurons became undetectable as a result of severe atrophy or was lost because of cell death. In contrast, overexpression of TrkB.FL did not result in a decrease in facial motor neuron number. Our results indicate that a subset of facial motor neurons remains dependent on TrkB ligands for the maintenance of structural and molecular characteristics in adulthood.

• Authors: Joris De Wit, Ruben Eggers, Robert Evers, Eero Castrén, Joost Verhaagen
• Journal: The Journal of neuroscience : the official journal of the Society for Neuroscience (J Neurosci) Vol. 26 Issue 5 Pg. 1516-30 (Feb 01 2006) ISSN: 1529-2401 [Electronic] United States
• PMID: 16452675 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Nerve Tissue Proteins
• Protein Isoforms
• Recombinant Fusion Proteins
• Receptor, trkB

Topics

• Animals
• Atrophy
• Cell Line
• Dendrites (ultrastructure)
• Dependovirus (genetics)
• Down-Regulation
• Facial Nerve (cytology)
• Gene Expression
• Genetic Vectors
• Humans
• Male
• Motor Neurons (metabolism, pathology)
• Nerve Degeneration (etiology, metabolism, pathology)
• Nerve Tissue Proteins (metabolism)
• Protein Isoforms (genetics, metabolism)
• Rats
• Rats, Wistar
• Receptor, trkB (genetics, metabolism, physiology)
• Recombinant Fusion Proteins (metabolism)
• Sequence Deletion
• Time Factors