Nutrients as trophic factors in neurons and the central nervous system: Role of retinoic acid

In multicellular organisms, death, survival, proliferation, and differentiation of a given cell depend on signals produced by neighboring and/or distant cells, resulting in the coordinated development and function of the various tissues. In the nervous system, control of cell survival and differentiation is achieved through the action of a distinct group of polypeptides collectively known as neurotrophic factors. Recent findings support the view that trophic factors also are involved in the response of the nervous system to acute injury. By contrast, nutrients are not traditionally viewed as potential trophic factors; however, there is increasing evidence that at least some influence neuronal differentiation. During development the brain is responsive to variations in nutrient supply, and this increased sensitivity or vulnerability of the brain to nutrient supply may reappear during neuronal repair, a period during which a rapid membrane resynthesis and reestablishment of synthetic pathways occur. To further evaluate the potential of specific nutrients to act as pharmacologic agents in the repair of injured neurons, the effects of retinoic acid, an active metabolite of vitamin A, and its role as a trophic factor are discussed. This literature review is intended to provide background information regarding the effect of retinoic acid on the cholinergic phenotype and the differentiation of these neurons and to explain how it may promote neuronal repair and survival following injury.