Regulation of Neuronal Differentiation by Retinoic Acid Alone and in Cooperation with Thyroid Hormone or Hydrocortisone

Abstract

Cultures highly enriched in neurons obtained from embryonic mouse cerebra were used to demonstrate that: (1) at the optimum concentration of 10^–8M retinoic acid stimulated the neurons to produce axon- and dentrite-like structures as determined by phase contrast and fluorescent microscopy; (2) the same concentration of retinoic acid stimulated acetyl cholinesterase and choline acetyltransferase activities; (3) treatment of neurons of either prenatal or neonatal equivalent age with retinoic acid produced a sustained stimulation of neuronal differentiation, and (4) retinoic acid cooperatively stimulated neuronal differentiation with either thyroid hormone or hydrocortisone.

A Complex Deoxyribonucleic Acid Response Element in the Rat Ca2+/Calmodulin-Dependent Protein Kinase IV Gene 5′-Flanking Region Mediates Thyroid Hormone Induction and Chicken Ovalbumin Upstream Promoter Transcription Factor 1 Repression

“…Iodine deficiency results in both maternal and fetal hypothyroidism, and the neurological manifestations of mental retardation and motor defects, as well as growth retardation, are irreversible after birth (4,5). Retinoic acid (RA) is required for normal development of the mammalian brain (6,7). Premature exposure to RA results in a high incidence of birth defects, especially in neural tubederived structures (8).…”

Synergistic stimulation of gamma-glutamyl transpeptidase and alkaline phosphatase activities by retinoic acid and astroglial factors in immortalized rat brain microvessel endothelial cells

“…Retinoic acid (RA), one of the main biologically active derivatives of retinol (vitamin A), has been shown to play an important role in the control of differentiation andor phenotypic expression of normal and malignant tissues in culture (Side11 et al, 1983;Sporn and Roberts, 1991;Ved and Pieringer, 1993;Song, 1994). Nuclear retinoic acid receptors (RARs) belong to the steroid hormone receptor superfamily of transcriptional regulators.…”

“…These results, taken together, suggest that retinoids may play an important role in the adult central nervous system and at the BBB level. Ved and Pieringer (1993) demonstrated that retinoic acid functions as an upregulator of the differentiation of neurons derived from brain, so we may expect that this substance could contribute to the differentiation of other cerebral cell types such as the brain microvessel endothelial cells.…”

Regulation of Neuronal Thyroid Hormone Receptor α₁ mRNA by Hydrocortisone, Thyroid Hormone and Retinoic Acid

“…The negative cooperativity demonstrated between RA and HC and especially between T3 and HC in the expres sion of TRa, mRNA is in striking contrast to the positive cooperativity between T3 and HC in the expression of proteolipid mRNA and myelin basic protein mRNA [5] and between RA and T3 in the expression of neuronalspecific enzymes [4], The fickled nature by which HC regulates myelin-associated compounds has already been noted [5], Whether a particular gene product will be up-or down-regulated by these three regulators, whose receptors share similar structural properties, is somewhat unpredictable at the moment. However, Glass et al [32] have demonstrated that the ability of their receptors to form various combinations of heterodimers greatly increases or decreases transcriptional activity, which in turn significantly increases the regulatory options expressed by these effectors.…”