Strain differences in the effects of chronic corticosterone exposure in the hippocampus.
Stress hormones are thought to be involved in the etiology of depression, in part, because animal models show they cause morphological damage to the brain, an effect that can be reversed by chronic antidepressant treatment. The current study examined two mouse strains selected for naturalistic variation of tissue regeneration after injury for resistance to the effects of chronic corticosterone (CORT) exposure on cell proliferation and neurotrophin mobilization. The wound healer MRL/MpJ and control C57BL/6J mice were implanted subcutaneously with pellets that released CORT for 7 days. MRL/MpJ mice were resistant to reductions of hippocampal cell proliferation by chronic exposure to CORT when compared to vulnerable C57BL/6J mice. Chronic CORT exposure also reduced protein levels of brain-derived neurotrophic factor (BDNF) in the hippocampus of C57BL/6J but not MRL/MpJ mice. CORT pellet exposure increased circulating levels of CORT in the plasma of both strains in a dose-dependent manner although MRL/MpJ mice may have larger changes from baseline. The strains did not differ in circulating levels of corticosterone binding globulin (CBG). There were also no strain differences in CORT levels in the hippocampus, nor did CORT exposure alter glucocorticoid receptor or mineralocorticoid receptor expression in a strain-dependent manner. Strain differences were found in the N-methyl-D-aspartate (NMDA) receptor, and BDNF I and IV promoters. Strain and CORT exposure interacted to alter tropomyosine-receptor-kinase B (TrkB) expression and this may be a potential mechanism protecting MRL/MpJ mice. In addition, differences in the inflammatory response of matrix metalloproteinases (MMPs) may also contribute to these strain differences in resistance to the deleterious effects of CORT to the brain.
Department of Psychiatry, University of Pennsylvania, Philadelphia, PA 19104, United States.
G E
GE
Hodes
B R
BR
Brookshire
T E
TE
Hill-Smith
S L
SL
Teegarden
O
O
Berton
I
I
Lucki
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D003345:Corticosterone / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004343:Drug Implants; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D015870:Gene Expression / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019463:Mice, Inbred MRL lpr; D060888:Real-Time Polymerase Chain Reaction; D011965:Receptors, Glucocorticoid / Q000096:biosynthesis; D013045:Species Specificity; D014156:Transcortin / Q000378:metabolism
D000928:Antidepressive Agents; D019208:Brain-Derived Neurotrophic Factor; D004343:Drug Implants; D011965:Receptors, Glucocorticoid; D014156:Transcortin; D003345:Corticosterone