Article

Strain differences in the effects of chronic corticosterone exposure in the hippocampus

Department of Psychiatry, University of Pennsylvania, Philadelphia, PA 19104, United States.
Neuroscience (Impact Factor: 3.33). 06/2012; 222:269-80. DOI: 10.1016/j.neuroscience.2012.06.017
Source: PubMed

ABSTRACT 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.

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    • "t mammals ( Grandel and Brand , 2013 ) . Even between different strains of mice responses in relation to stress can be importantly different . After 7 days exposure to high corticosterone levels hippocampal cell proliferation in MRL / MpJ mice stayed unaltered while cell proliferation and BDNF levels in C57BL / 6J mice were significantly reduced ( Hodes et al . , 2012 ) . Taken together this explanation of species - specific or even strain specific potential for regeneration forms a broad and general interpretation . Conse - quently it is less useful for explaining the typical OBX related rat / mouse differences . However , it should make us cautious in relying too much on the findings in one species"
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