Susceptibility to stress in transgenic mice overexpressing TrkC, a model of panic disorder.
Stressful life events increase the susceptibility for subsequent onset of psychiatric disorders in humans. Previous research has implicated neurotrophins in the onset of some stress-related diseases, such as major depression disorder, post-traumatic stress disorder or panic disorder. We have tested the hypothesis that the neurotrophin-3 (NT-3)/TrkC system is a genetic interface mediating the deleterious effects of stress on the initiation of panic disorder and other pathologies. To this aim, we have analyzed the functionality of HPA axis and the behavioral consequences of different types of stressful conditions in a mouse model of panic disorder, which overexpresses TrkC, the high affinity-receptor for NT-3 (TgNTRK3). Our results reveal that TgNTRK3 mice exhibit an altered circadian corticosterone rhythm that is reversed by clonidine treatment, but normal expression of genes involved in the control of the hypothalamus-pituitary-adrenal (HPA) axis (CRH, GR) and normal corticosterone response to acute and chronic stressors. In contrast, they exhibit an altered pattern of activation of stress-related brain areas and showed enhanced anxiety-related behavior and more passive strategies than wild types under some chronic stress conditions. We conclude that TgNTRK3 mice present differences in their response to stress characterized by subtle changes in the HPA axis, marked changes in acute stress-induced brain activation and altered coping strategies, suggesting a key role of TrkC receptor in the stress neural circuitry and in the behavioral consequences of chronic stress.
Amador-Arjona
Alejandro
A
Genes and Disease Program, Centre for Genomic Regulation, Universidad Pompeu Fabra, Barcelona Biomedical Research Park (PRBB), Dr. Aiguader 88, Barcelona E-08003, Spain.
Delgado-Morales
Raúl
R
Belda
Xavier
X
Gagliano
Humberto
H
Gallego
Xavier
X
Keck
Martin E
ME
Armario
Antonio
A
Dierssen
Mara
M
D000818:Animals; D001007:Anxiety / Q000235:genetics*; D001522:Behavior, Animal / Q000502:physiology; D002940:Circadian Rhythm / Q000502:physiology; D003345:Corticosterone / Q000502:physiology; D004195:Disease Models, Animal; D020022:Genetic Predisposition to Disease; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology; D051379:Mice; D008822:Mice, Transgenic; D009414:Nerve Growth Factors / Q000378:metabolism*; D016584:Panic Disorder / Q000235:genetics* / Q000503:physiopathology; D010913:Pituitary-Adrenal System / Q000503:physiopathology; D020812:Receptor, trkC / Q000235:genetics* / Q000378:metabolism; D013315:Stress, Psychological / Q000235:genetics*
D009414:Nerve Growth Factors; C518911:neurotropin 3, mouse; D020812:Receptor, trkC; D003345:Corticosterone