DISTRIBUTION OF RETINOIC ACID RECEPTOR-BETA PROTEINS IN RAT-BRAIN - UP-REGULATION BY RETINOIC ACID

While retinoic acid is known to be involved in the neurogenesis of embryos, little is known about its function in the adult brain despite the fact that many retinols and retinoic acid binding activities were detected in the extracts from mature rat brain. Furthermore, retinoic acid that was injected into peritoneal cavities was incorporated into the brain as well as into the testis and liver. By using immunoblot analyses with specific antisera against three retinoic acid receptors, alpha, beta and gamma, we demonstrated that the beta type is the main retinoic acid receptor expressed in the mature rat brain. Retinoic acid receptor beta proteins were expressed at a higher level in the cerebral cortex, striatum and cerebellum than in the other regions, and low levels were found in the limbic forebrain and hippocampus. In the cerebellum, granular cells were most strongly positive for retinoic acid receptor beta. The amount of retinoic acid receptor beta proteins in the cerebellum was reduced in rats fed with a vitamin A-deficient diet, and they were up-regulated at 12 h after the injection of retinoic acid into the peritoneal cavity. Immunohistochemical studies supported the immunoblot data; granular cells were negative for retinoic acid receptor beta in a vitamin A-deficient rat, but they became positive after the injection of retinoic acid. These findings suggest that retinoic acid receptor beta is involved in the physiological functions of the granular cells in the cerebellum and that these functions are regulated by the retinoic acid concentration in the adult brain.