Vitamin A deficiency impairs contextual fear memory in rats: Abnormalities in the glucocorticoid pathway
J Neuroendocrinol. 2019-11-01; 31(11):
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Bonhomme D(1)(2), Alfos S(1)(2)(3), Webster SP(4), Wolff M(5)(6), Pallet V(1)(2)(3), Touyarot K(1)(2)(3).
(1)UMR 1286, Nutrition et Neurobiologie Intégrée, Université de Bordeaux, Bordeaux, France.
(2)Nutrition et Neurobiologie Intégrée, UMR 1286, Institut National de la Recherche Agronomique (INRA), Bordeaux, France.
(3)Nutrition et Neurobiologie Intégrée, UMR 1286, Bordeaux INP, Bordeaux, France.
(4)The Queen’s Medical Research Institute, Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK.
(5)UMR 5287, CNRS, INCIA, Bordeaux, France.
(6)UMR 5287, INCIA, Université de Bordeaux, Bordeaux, France.
Vitamin A and its active metabolite, retinoic acid (RA), play a key role in the
maintenance of cognitive functions in the adult brain. Depletion of RA using the
vitamin A deficiency (VAD) model in Wistar rats leads to spatial memory deficits
in relation to elevated intrahippocampal basal corticosterone (CORT) levels and
increased hippocampal 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1)
activity. All of these effects are normalised by vitamin A supplementation.
However, it is unknown whether vitamin A status also modulates contextual fear
conditioning (CFC) in a glucocorticoid-associated fear memory task dependent on
the functional integrity of the hippocampus. In the present study, we
investigated the impact of VAD and vitamin A supplementation in adult male rats
on fear memory processing, plasma CORT levels, hippocampal retinoid receptors and
11β-HSD1 expression following a novelty-induced stress. We also examined whether
vitamin A supplementation or a single injection of UE2316, a selective 11β-HSD1
inhibitor, known to modulate local glucocorticoid levels, had any beneficial
effects on contextual fear memory and biochemical parameters in VAD rats. We
provide evidence that VAD rats exhibit a decreased fear conditioning response
during training with a poor contextual fear memory 24 hours later. These
VAD-induced cognitive impairments are associated with elevated plasma CORT levels
under basal conditions, as well as following a stressful event, with saturated
CORT release, altered hippocampal retinoid receptors and 11β-HSD1 expression.
Vitamin A supplementation normalises VAD-induced fear conditioning training
deficits and all biochemical effects, although it cannot prevent fear memory
deficits. Moreover, a single injection of UE2316 not only impairs contextual fear
memory, but also reduces plasma CORT levels, regardless of the vitamin A status
and decreases slightly hippocampal 11β-HSD1 activity in VAD rats following
stress. The present study highlights the importance of vitamin A status with
respect to modulating fear memory conditioning in relation to plasma CORT levels
and hippocampal 11β-HSD1.
© 2019 British Society for Neuroendocrinology.