The rhythm of retinoids in the brain

Abstract

The retinoids are a family of compounds that in nature are derived from vitamin A or pro-vitamin A carotenoids. An essential part of the diet for mammals, vitamin A has long been known to be essential for many organ systems in the adult. More recently, however, they have been shown to be necessary for function of the brain and new discoveries point to a central role in processes ranging from neuroplasticity to neurogenesis. Acting in several regions of the central nervous system including the eye, hippocampus and hypothalamus, one common factor in its action is control of biological rhythms. This review summarizes the role of vitamin A in the brain; its action through the metabolite retinoic acid via specific nuclear receptors, and the regulation of its concentration through controlled synthesis and catabolism. The action of retinoic acid to regulate several rhythms in the brain and body, from circadian to seasonal, is then discussed to finish with the importance of retinoic acid in the regular pattern of sleep.We review the role of vitamin A and retinoic acid (RA) as mediators of rhythm in the brain. In the suprachiasmatic nucleus and hippocampus they control expression of circadian clock genes while in the cortex retinoic acid is required for delta oscillations of sleep. Retinoic acid is also central to a second rhythm that keeps pace with the seasons, regulating function in the hypothalamus and pineal gland.

Generating retinoic acid gradients by local degradation during craniofacial development: One cell's cue is another cell's poison

“…RA has well‐documented roles in cell growth, patterning, fate specification, and differentiation, apoptosis, immune response, and maintaining circadian rhythms (Gudas & Wagner, ; Mora, Iwata, & von AndriIwata, ; Ransom, Morgan, McCaffery, & Stoney, ; Teletin, Vernet, Ghyselinck, & Mark, ). During development it is considered especially critical for the formation of the vertebrate head.…”

Mechanisms of retinoic acid signalling and its roles in organ and limb development

“…RA regulates development by acting as a diffusible signalling molecule that controls the activity of a family of RARs (reviewed in REFS 13,14). Moreover, RA is essential in adults for maintenance of epithelial homeostasis 15 , and for spermatogenesis 16 , immune function 17 and brain function 18 .…”

Comparison of the ligand binding site of CYP2C8 with CYP26A1 and CYP26B1: a structural basis for the identification of new inhibitors of the retinoic acid hydroxylases

“…Retinoic acid is a highly regulated signaling molecule that is involved in a host of dermatological, immunological and neurological functions through binding to the retinoic acid receptors and retinoid X receptors 12,13,[78][79][80][81][82] . As such, the metabolic pathways that are involved in the regulation of retinoic acid represent potential targets that can be exploited to alter concentrations of retinoic acid in vivo.…”