Vitamin A status regulates glucocorticoid availability in Wistar rats: consequences on cognitive functions and hippocampal neurogenesis?

Damien Bonhomme,Marie-Pierre Moisan,Pascale Roux,Paul Higueret,Amandine M. Minni,Emmanuel Richard,Véronique Pallet,Serge Alfos,Katia Touyarot

doi:10.3389/fnbeh.2014.00020

Abstract

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.

Highlights

The vitamin A, through its main metabolite retinoic acid (RA), plays a key role in cognitive functions and in anxiety-like behavior and hippocampus-dependent memory during adulthood (Lane and Bailey, 2005; McCaffery et al, 2006; Cai et al, 2010; Olson and Mello, 2010)
A vitamin A supplementation during 4 weeks was sufficient to induce a significant increase of body weight in Vitamin A Deficiency (VAD) rats while it did not affect the weight of control rats [Three-Way ANOVA between 11 and 14 weeks of VAD, deficiency × supplementation × weeks: F(3, 99)=52.20, p < 0.001]
We have shown that VAD in Wistar rats can increase HPA axis activity leading to hypersecretion of basal free plasma CORT level that is normalized by a vitamin A supplementation

Summary

Introduction

The vitamin A, through its main metabolite retinoic acid (RA), plays a key role in cognitive functions and in anxiety-like behavior and hippocampus-dependent memory during adulthood (Lane and Bailey, 2005; McCaffery et al, 2006; Cai et al, 2010; Olson and Mello, 2010). A disruption of RA signaling pathway has been involved in age-related memory decline (Etchamendy et al, 2001; Mingaud et al, 2008). In these studies life-long nutritional vitamin A supplementation or RA treatment corrected memory deficits in aged rodents. VAD disrupted hippocampal long-term potentiation (Misner et al, 2001; Jiang et al, 2012), hippocampal neurogenesis (Jacobs et al, 2006) and induced spatial and relational memory deficits (Cocco et al, 2002; Etchamendy et al, 2003). We have recently demonstrated that VAD-induced hippoccampal neurogenesis alterations and spatial memory deficits could be corrected by RA treatment (Bonnet et al, 2008)

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