Critical role of plasma corticosteroid-binding-globulin during stress to promote glucocorticoid delivery to the brain: impact on memory retrieval.

Amandine M. Minni, Rodolphe Dorey, Christophe Piérard, Gaëlle Dominguez, Jean-Christophe Helbling, Aline Foury, Daniel Béracochéa, Marie-Pierre Moisan
Endocrinology. 2012-10-01; 153(10): 4766-4774
DOI: 10.1210/en.2012-1485

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We aimed at demonstrating that corticosteroid binding globulin (CBG), a plasma
glycoprotein binding glucocorticoids with high affinity in blood, endorses a
major role under stress conditions by regulating free glucocorticoid access to
the brain and thereby influences glucocorticoid-dependent behaviors. Hence, we
compared CBG-deficient mice (Cbg-/-) and their controls (Cbg+/+) in a specific
memory task, i.e. the delayed alternation behavior, requiring memory retrieval
both under stress and nonstress conditions and previously shown to be dependent
on hippocampal glucocorticoid levels. Our results evidence that Cbg-/- mice,
unlike controls, remain insensitive to stress applied before memory retrieval.
Furthermore, under stress conditions, we observed a blunted surge of
corticosterone (CORT) in plasma and no free CORT rise in the hippocampus of
Cbg-/-. Moreover, intrahippocampal infusion of CORT through implanted cannulae
was used to mimic stress CORT rise before memory retrieval. This infusion of CORT
reproduced memory retrieval impairments in Cbg-/- as in Cbg+/+ controls. Finally,
we provide evidence that Cbg-/- mice exhibit a normal adrenal response to stress
and ACTH. Given that CBG deficiency is known to markedly impact on CORT clearance
from plasma, our current article demonstrates that Cbg-/- insensitivity in memory
retrieval after stress results from the blunted CORT response due to increased
CORT clearance. Overall, our data suggest that the impact of CBG genetic
deficiency on various behavioral patterns reported previously stems from a
smaller CORT reservoir in blood. Inasmuch as CBG discloses interindividual
variations, such a parameter ought to be taken into account when studying
stress-induced glucocorticoid action in brain.


Auteurs Bordeaux Neurocampus