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

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.

Acute dietary tryptophan manipulation differentially alters social behavior, brain serotonin and plasma corticosterone in three inbred mouse strains

“…Specifically, vitamin A, D, and E contents were greater in purified diets. Vitamin A deficiency has anxiogenic effects (Bonhomme et al, 2014), and E deficiency alters CORT release in rats (Terada et al, 2011). Vitamin D influences sniffing and following (Kalueff et al, 2006), and can modulate 5-HT synthesis (Patrick and Ames, 2014).…”

On the role of skin in the regulation of local and systemic steroidogenic activities

“…Mice lacking RARα, RARγ, RXRα, and RXRβ display profound anomalies in gonadal, adrenal, and epidermal functions, including sterility and/or embryonic lethality [219–222]. Also, retinoid metabolism and signaling are frequently decreased with many age-related complications and diseases [223–226]. Systemic administration of RA reverses most reproductive and developmental blocks in vitamin A deficient (VAD) rats/mice induced either by nutritional or genetic approaches, demonstrating that retinoid signaling rescues reproductive defects in VAD animals [220, 222, 227].…”

Vitamin A deficiency impairs contextual fear memory in rats: Abnormalities in the glucocorticoid pathway

“…Then, half of the vitamin A deficient rats (n = 10) and half of the control rats (n = 10) were supplemented with a vitamin A‐enriched diet (20 IU retinol g –1 ) during the next 4 weeks until they were killed: these groups were referred to as VAD + Vit A and Control + Vit A, respectively, whereas the other half were kept on their respective diets. The supplemented vitamin A diet (20 IU retinol g –1 ) was used because it has been shown to be effective in reversing VAD‐related memory decline . Thus, 12 weeks after their arrival, rats were trained and tested in a contextual fear conditioning task.…”

“…More recently, the potential role of glucocorticoid signalling on VAD‐induced cognitive impairments has emerged . It is well‐established that glucocorticoid (GC; corticosterone in rodents and cortisol in humans) hormones induce inverted U‐shaped dose effects on different memory processes .…”

“…We have recently demonstrated that excess basal intrahippocampal corticosterone (CORT) levels probably resulting from both elevated free basal plasma CORT levels and hyperactivity of hippocampal 11β‐HSD1 could contribute to spatial memory deficits in VAD rats . Interestingly, vitamin A supplementation can suppress spatial memory deficits and hippocampal neurogenesis alterations in VAD rats, possibly by decreasing basal intrahippocampal CORT levels.…”