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

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 en...

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Detalles Bibliográficos
Autores: Dierssen, Mara|||0000-0003-0853-6865, Gratacòs, Mònica|||0000-0001-7304-7289, Sahún, Ignasi, Martin, Miquel|||0000-0001-7771-611X, Gallego, Xavier, Amador-Arjona, Alejandro, Martínez de Lagrán, María|||0000-0002-0836-6491, Murtra, Patricia, Martí, Eulàlia|||0000-0002-1030-3158, Pujana, Miguel Angel|||0000-0003-3222-4044, Ferrer, Isidro|||0000-0001-9888-8754, Dalfo, Esther|||0000-0003-4677-8515, Martínez-Cué, Carmen, Flórez, Jesús, Torres-Peraza, Jesús F., Alberch i Vié, Jordi|||0000-0002-8684-2721, Maldonado, Rafael|||0000-0002-4359-8773, Fillat, Cristina|||0000-0002-0801-3338, Estivill, Xavier|||0000-0002-0723-2256
Tipo de recurso: artículo
Fecha de publicación:2006
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:166638
Acceso en línea:https://ddd.uab.cat/record/166638
https://dx.doi.org/urn:doi:10.1016/j.nbd.2006.07.015
Access Level:acceso abierto
Palabra clave:Panic disorder
NT-3
TrkC
Anxiety-like behavior
Mouse defense test battery
Locus coeruleus
Descripción
Sumario: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.

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