Abstract
A dysfunction of retinoid hippocampal signaling pathway has been involved in the appearance of affective and cognitive disorders. However, the underlying neurobiological mechanisms remain unknown. Hippocampal granule neurons are generated throughout life and are involved in emotion and memory. Here, we investigated the effects of vitamin A deficiency (VAD) on neurogenesis and memory and the ability of retinoic acid (RA) treatment to prevent VAD-induced impairments. Adult retinoid-deficient rats were generated by a vitamin A-free diet from weaning in order to allow a normal development. The effects of VAD and/or RA administration were examined on hippocampal neurogenesis, retinoid target genes such as neurotrophin receptors and spatial reference memory measured in the water maze. Long-term VAD decreased neurogenesis and led to memory deficits. More importantly, these effects were reversed by 4 weeks of RA treatment. These beneficial effects may be in part related to an up-regulation of retinoid-mediated molecular events, such as the expression of the neurotrophin receptor TrkA. We have demonstrated for the first time that the effect of vitamin A deficient diet on the level of hippoccampal neurogenesis is reversible and that RA treatment is important for the maintenance of the hippocampal plasticity and function.
Highlights
Vitamin A deficiency (VAD), leading to retinoic acid (RA) hyposignaling, represents a major public health problem and is estimated to affect 200 million children and adults in many countries [1,2]
A quantitative analysis revealed that 11 weeks of VAD or RA treatment has no effect on the number of newly generated neurons [Fig. 3B, F(3,29) = 1.51,p = 0.23]
The results of the present experiments show that 14 weeks of VAD decreases hippocampal neurogenesis, based on the numbers of doublecortin-IR cells, and impairs spatial memory
Summary
Vitamin A deficiency (VAD), leading to retinoic acid (RA) hyposignaling, represents a major public health problem and is estimated to affect 200 million children and adults in many countries [1,2]. The naturally occurring hypoactivity of the retinoid signaling pathway induces spatial memory and hippocampal long term potentiation deficits, which are alleviated by the normalization of brain retinoid signaling with RA treatment or nutritional vitamin A supplementation [20,21]. Despite these striking relationships between retinoid signaling and memory, the mechanisms by which hippocampal retinoid hyposignaling influence learning abilities remain largely unknown
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