Transgenic mice overexpressing the full-length neurotrophin receptor TrkC exhibit increased catecholaminergic neuron density in specific brain areas and increased anxiety-like behavior and panic reaction

Mara Dierssen, Mònica Gratacòs, Ignasi Sahún, Miguel Martín, Xavier Gallego, Alejandro Amador-Arjona, María Martínez de Lagrán, Patricia Murtra, Eulalia Martí, Miguel A. Pujana, Isidre Ferrer, Esther Dalfó, Carmen Martínez-Cué, Jesús Flórez, Jesús F. Torres-Peraza, Jordi Alberch, Rafael Maldonado, Cristina Fillat, Xavier Estivill

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34 Citations (Scopus)

Abstract

Accumulating evidence has suggested that neurotrophins participate in the pathophysiology of mood disorders. We have developed transgenic mice overexpressing the full-length neurotrophin-3 receptor TrkC (TgNTRK3) in the central nervous system. TgNTRK3 mice show increased anxiety-like behavior and enhancement of panic reaction in the mouse defense test battery, along with an increase in the number and density of catecholaminergic (tyrosine hydroxylase positive) neurons in locus coeruleus and substantia nigra. Furthermore, treatment of TgNTRK3 mice with diazepam significantly attenuated the anxiety-like behaviors in the plus maze. These results provide evidence for the involvement of TrkC in the development of noradrenergic neurons in the central nervous system with consequences on anxiety-like behavior and panic reaction. Thus, changes in TrkC expression levels could contribute to the phenotypic expression of panic disorder through a trophic effect on noradrenergic neurons in the locus coeruleus. Our results demonstrate that the elevated NT3-TrkC tone via overexpression of TrkC in the brain may constitute a molecular mechanism for the expression of anxiety and anxiety.

Original languageEnglish
Pages (from-to)403-418
Number of pages16
JournalNeurobiology of Disease
Volume24
Issue number2
DOIs
Publication statusPublished - 1 Nov 2006

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Keywords

  • Anxiety-like behavior
  • Locus coeruleus
  • Mouse defense test battery
  • NT-3
  • Panic disorder
  • TrkC

ASJC Scopus subject areas

  • Neurology

Cite this

Dierssen, M., Gratacòs, M., Sahún, I., Martín, M., Gallego, X., Amador-Arjona, A., Martínez de Lagrán, M., Murtra, P., Martí, E., Pujana, M. A., Ferrer, I., Dalfó, E., Martínez-Cué, C., Flórez, J., Torres-Peraza, J. F., Alberch, J., Maldonado, R., Fillat, C., & Estivill, X. (2006). Transgenic mice overexpressing the full-length neurotrophin receptor TrkC exhibit increased catecholaminergic neuron density in specific brain areas and increased anxiety-like behavior and panic reaction. Neurobiology of Disease, 24(2), 403-418. https://doi.org/10.1016/j.nbd.2006.07.015