Daily patterns of clock and cognition‐related factors are modified in the hippocampus of vitamin A‐deficient rats

Abstract

The circadian expression of clock and clock-controlled cognition-related genes in the hippocampus would be essential to achieve an optimal daily cognitive performance. There is some evidence that retinoid nuclear receptors (RARs and RXRs) can regulate circadian gene expression in different tissues. In this study, Holtzman male rats from control and vitamin A-deficient groups were sacrificed throughout a 24-h period and hippocampus samples were isolated every 4 or 5 h. RARα and RXRβ expression level was quantified and daily expression patterns of clock BMAL1, PER1, RORα and REVERB genes, RORα and REVERB proteins, as well as temporal expression of cognition-related RC3 and BDNF genes were determined in the hippocampus of the two groups of rats. Our results show significant daily variations of BMAL1, PER1, RORα and REVERB genes, RORα and REVERB proteins and, consequently, daily oscillating expression of RC3 and BDNF genes in the rat hippocampus. Vitamin A deficiency reduced RXRβ mRNA level as well as the amplitude of PER1, REVERB gene and REVERB protein rhythms, and phase-shifted the daily peaks of BMAL1 and RORα mRNA, RORα protein and RC3 and BDNF mRNA levels. Thus, nutritional factors, such as vitamin A and its derivatives the retinoids, might modulate daily patterns of BDNF and RC3 expression in the hippocampus and they could be essential to maintain an optimal daily performance at molecular level in this learning-and-memory-related brain area.

Third Trimester-Equivalent Ethanol Exposure Is Characterized by an Acute Cellular Stress Response and an Ontogenetic Disruption of Genes Critical for Synaptic Establishment and Function in Mice

“…This role in spatial learning is consistent in many studies, with retinoic acid signaling implicated in changes to long-term potentiation, hippocampal synaptic function, and impairments to working memory [68,69]. Interestingly, these impairments in cognition are also correlated with altered circadian clock patterns [70], which has been identified by this study as a potential short-term target of ethanol exposure during synaptogenesis (tables 3, 4; fig. 5).…”

Circadian Synchronization of Cognitive Functions

“…Maximal RC3 expression occurs at the end of the night preceding BDNF mRNA peak, as in the cellular events which occurs for postsynaptic activation [ 38 ]. As expected, BDNF and RC3 rhythms are in phase with the circadian clock, BMAL1 and Per1, protein levels as well as with the maximal antioxidant enzyme activity shown by Fonzo and colleagues [ 39 ].…”

“…11.2 ) and to propose the existence of a temporally well-orchestrated RC3 and BDNF cycle underlying temporal patterns of synaptic plasticity in the hippocampus [ 38 ].…”

Daily rhythms of catalase and glutathione peroxidase expression and activity are endogenously driven in the hippocampus and are modified by a vitamin A-free diet

“…Consistently with what we previously observed, 41 the VAD phase-shifted circadian RXRγ mRNA rhythm, in this brain area. Thus, we suggest the nutritional VAD might change the circadian rhythms' acrophase of memory-related, RA-target genes, such as the brain-derived neurotrophic factor (BDNF) and neurogranin (RC3), 49 by modifying the phase of the circadian patterns of retinoid receptors expression.…”