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 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.
Dierssen
Mara
M
Genes and Disease Program, Genomic Regulation Center (CRG-UPF), Barcelona, Biomedical Research Park, E-08003 Barcelona, Catalonia, Spain. mara.dierssen@crg.es
Gratacòs
Mònica
M
Sahún
Ignasi
I
Martín
Miguel
M
Gallego
Xavier
X
Amador-Arjona
Alejandro
A
Martínez de Lagrán
María
M
Murtra
Patricia
P
Martí
Eulalia
E
Pujana
Miguel A
MA
Ferrer
Isidre
I
Dalfó
Esther
E
Martínez-Cué
Carmen
C
Flórez
Jesús
J
Torres-Peraza
Jesús F
JF
Alberch
Jordi
J
Maldonado
Rafael
R
Fillat
Cristina
C
Estivill
Xavier
X
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
D002395:Catecholamines; D020812:Receptor, trkC; D009638:Norepinephrine