title: 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.
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.
authors.affiliation: Genes and Disease Program, Genomic Regulation Center (CRG-UPF), Barcelona, Biomedical Research Park, E-08003 Barcelona, Catalonia, Spain. mara.dierssen@crg.es
authors.forename: Mara
authors.initials: M
authors.lastname: Dierssen
authors.forename: Mònica
authors.initials: M
authors.lastname: Gratacòs
authors.forename: Ignasi
authors.initials: I
authors.lastname: Sahún
authors.forename: Miguel
authors.initials: M
authors.lastname: Martín
authors.forename: Xavier
authors.initials: X
authors.lastname: Gallego
authors.forename: Alejandro
authors.initials: A
authors.lastname: Amador-Arjona
authors.forename: María
authors.initials: M
authors.lastname: Martínez de Lagrán
authors.forename: Patricia
authors.initials: P
authors.lastname: Murtra
authors.forename: Eulalia
authors.initials: E
authors.lastname: Martí
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Pujana
authors.forename: Isidre
authors.initials: I
authors.lastname: Ferrer
authors.forename: Esther
authors.initials: E
authors.lastname: Dalfó
authors.forename: Carmen
authors.initials: C
authors.lastname: Martínez-Cué
authors.forename: Jesús
authors.initials: J
authors.lastname: Flórez
authors.forename: Jesús F
authors.initials: JF
authors.lastname: Torres-Peraza
authors.forename: Jordi
authors.initials: J
authors.lastname: Alberch
authors.forename: Rafael
authors.initials: R
authors.lastname: Maldonado
authors.forename: Cristina
authors.initials: C
authors.lastname: Fillat
authors.forename: Xavier
authors.initials: X
authors.lastname: Estivill
mesh_terms: D000818:Animals; D001008:Anxiety Disorders / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D001342:Autonomic Nervous System Diseases / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D001522:Behavior, Animal / Q000502:physiology; D001921:Brain / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D002395:Catecholamines / Q000378:metabolism*; D002452:Cell Count; D049109:Cell Proliferation; D004195:Disease Models, Animal; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D008125:Locus Coeruleus / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009434:Neural Pathways / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D009474:Neurons / Q000378:metabolism*; D009483:Neuropsychological Tests; D009638:Norepinephrine / Q000378:metabolism; D016584:Panic Disorder / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D020812:Receptor, trkC / Q000235:genetics / Q000378:metabolism*; D013378:Substantia Nigra / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D015854:Up-Regulation / Q000235:genetics
chemical_list: D002395:Catecholamines; D020812:Receptor, trkC; D009638:Norepinephrine