Stress-resistant mice overexpressing glucocorticoid receptors display enhanced BDNF in the amygdala and hippocampus with unchanged NGF and serotonergic function.
Dysfunctional glucocorticoid receptor (GR) signaling has been shown to be involved in the pathogenesis of depressive behavior in mice and humans. In accordance with this hypothesis GR overexpressing mice are less susceptible to develop depressive-like behavior when subjected to stressful events. Here, we analyzed GR overexpressing mice for morning and evening content of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and the tissue levels of serotonin and its metabolite 5-hydroxyindoleacetic acid) in brain areas suspected to be involved in stress adaptation. BDNF concentrations in the hippocampus and amygdala/piriform cortex were significantly enhanced in GR overexpressing mice (by maximally +103%) compared to wildtype animals. Diurnal variations, as detected for NGF in the hypothalamus, for BDNF in the frontal cortex and striatum and for serotonergic function in the frontal cortex and hypothalamus, were not affected by the genotype. In conclusion, GR overexpression-dependent increases of hippocampal and amygdala BDNF content presumably represent a dynamic correlate of enhanced stress resistance.
Schulte-Herbrüggen
Olaf
O
Department of Psychiatry and Psychotherapy, Charité-University Medicine Berlin, Campus Benjamin Franklin, Eschenallee 3, 14050 Berlin, Germany.
Chourbaji
Sabine
S
Ridder
Stephanie
S
Brandwein
Christiane
C
Gass
Peter
P
Hörtnagl
Heide
H
Hellweg
Rainer
R
D000679:Amygdala / Q000737:chemistry*; D000818:Animals; D015306:Biogenic Monoamines / Q000032:analysis / Q000378:metabolism; D001923:Brain Chemistry; D019208:Brain-Derived Neurotrophic Factor / Q000032:analysis*; D002940:Circadian Rhythm; D003345:Corticosterone / Q000097:blood; D005260:Female; D006624:Hippocampus / Q000737:chemistry*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009414:Nerve Growth Factors / Q000032:analysis*; D011965:Receptors, Glucocorticoid / Q000235:genetics*; D012701:Serotonin / Q000032:analysis / Q000502:physiology*; D013312:Stress, Physiological / Q000235:genetics*
D015306:Biogenic Monoamines; D019208:Brain-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D011965:Receptors, Glucocorticoid; D012701:Serotonin; D003345:Corticosterone