Differential regulation of neurotrophins and serotonergic function in mice with genetically reduced glucocorticoid receptor expression.
The neurotrophin and serotonin (5-HT) hypotheses of depression were studied in a mouse model of reduced glucocorticoid receptor (GR) function (GR(+/-) mice), which recently has been proven as a murine model of predisposition for depressive behaviour under stressful conditions. In this model we studied diurnal changes in neurotrophins and serotonergic function in candidate brain regions mediating depressive behaviour. Morning and evening levels of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), 5-HT and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) were analyzed in representative brain regions of GR(+/-) and wildtype mice. The diurnal variation of hippocampal BDNF in wildtypes with higher levels in the morning was absent in GR(+/-) mice. Hypothalamus and parietal cortex displayed enhanced BDNF levels in GR(+/-) mice. In the frontal cortex, striatum and hypothalamus NGF increased from morning to evening in both genotypes, with an exaggeration in GR(+/-) mice. The diurnal variation of 5-HT levels and turnover did not differ significantly between genotypes. It was only in the hypothalamus that the evening level of 5-HIAA was lower in GR(+/-) mice than in wildtype mice. In conclusion, the present data indicate a contribution of altered BDNF and NGF protein levels to the predisposition for depressive behaviour in the GR(+/-) mouse model of depression, but argue against an eminent role of the serotonergic system.
Schulte-Herbrüggen
Olaf
O
Department of Psychiatry and Psychotherapy, Charité-University Medicine Berlin, Campus Benjamin Franklin, Berlin, Germany.
Hellweg
Rainer
R
Chourbaji
Sabine
S
Ridder
Stephanie
S
Brandwein
Christiane
C
Gass
Peter
P
Hörtnagl
Heide
H
D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002940:Circadian Rhythm; D003345:Corticosterone / Q000097:blood; D003863:Depression / Q000209:etiology / Q000378:metabolism*; D004198:Disease Susceptibility; D006824:Hybridization, Genetic; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D020932:Nerve Growth Factor / Q000378:metabolism; D009414:Nerve Growth Factors / Q000378:metabolism*; D011965:Receptors, Glucocorticoid / Q000172:deficiency*; D012701:Serotonin / Q000378:metabolism*; D014018:Tissue Distribution
D015306:Biogenic Monoamines; D019208:Brain-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D011965:Receptors, Glucocorticoid; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D020932:Nerve Growth Factor; D003345:Corticosterone