Vitamin A status regulates glucocorticoid availability in Wistar rats: consequences on cognitive functions and hippocampal neurogenesis?
Front. Behav. Neurosci.. 2014-01-01; 8:
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1. Front Behav Neurosci. 2014 Feb 4;8:20. doi: 10.3389/fnbeh.2014.00020. eCollection
Vitamin A status regulates glucocorticoid availability in Wistar rats:
consequences on cognitive functions and hippocampal neurogenesis?
Bonhomme D(1), Minni AM(1), Alfos S(1), Roux P(1), Richard E(2), Higueret P(1),
Moisan MP(1), Pallet V(1), Touyarot K(1).
(1)INRA, Nutrition et Neurobiologie Intégrée (NutriNeuro), UMR 1286 Bordeaux,
France ; University of Bordeaux, Nutrition et Neurobiologie Intégrée
(NutriNeuro), UMR 1286 Bordeaux, France.
(2)INSERM, Biothérapie des Maladies Génétiques et Cancer, U1035 Bordeaux, France.
A disruption of the vitamin A signaling pathway has been involved in age-related
memory decline and hippocampal plasticity alterations. Using vitamin A deficiency
(VAD), a nutritional model leading to a hyposignaling of the retinoid pathway, we
have recently demonstrated that retinoic acid (RA), the active metabolite of
vitamin A, is efficient to reverse VAD-induced spatial memory deficits and adult
hippocampal neurogenesis alterations. Besides, excess of glucocorticoids (GCs)
occurring with aging is known to strongly inhibit hippocampal plasticity and
functions and few studies report on the counteracting effects of RA signaling
pathway on GCs action. Here, we have addressed whether the modulation of brain
GCs availability could be one of the biological mechanisms involved in the
effects of vitamin A status on hippocampal plasticity and functions. Thus, we
have studied the effects of a vitamin A-free diet for 14 weeks and a 4-week
vitamin A supplementation on plasma and hippocampal corticosterone (CORT) levels
in Wistar rats. We have also investigated corticosteroid binding globulin (CBG)
binding capacity and 11beta-Hydrosteroid Dehydrogenase type 1 (11β-HSD1)
activity, both important modulators of CORT availability at the peripheral and
hippocampal levels respectively. Interestingly, we show that the vitamin A status
regulates levels of free plasma CORT and hippocampal CORT levels, by acting
through a regulation of CBG binding capacity and 11β-HSD1 activity. Moreover, our
results suggest that increased CORT levels in VAD rats could have some
deleterious consequences on spatial memory, anxiety-like behavior and adult
hippocampal neurogenesis whereas these effects could be corrected by a vitamin A
supplementation. Thus, the modulation of GCs availability by vitamin A status is
an important biological mechanism that should be taken into account in order to
prevent age-related cognitive decline and hippocampal plasticity alterations.