Localization of cellular retinoid-binding proteins suggests specific roles for retinoids in the adult central nervous system

Abstract

Retinoic acid, the active metabolite of retinoids (vitamin A compounds), is thought to act as a gene regulator via ligand-activated transcription factors. In order to investigate possible roles of retinoids and retinoid-controlled gene expression in brain function, we have used immunohistochemistry to localize the possible presence of two intracellular retinoid-binding proteins, cellular retinol-binding protein type I and cellular retinoic acid-binding protein type I, in the adult rat central nervous system. We find a widespread, yet distinct, presence of these two binding proteins in the brain and spinal cord. Most of the immunoreactivity is neuronal, including cell somata, as well as dendritic and axonal processes and axon terminals. Cellular retinol-binding protein type I-immunoreactivity is also found in the walls of cerebral blood vessels, the meninges, the choroid plexus, certain ependymal cells, tanocytes and certain other glial elements. The cellular retinol-binding protein type I- and cellular retinoic acid-binding protein type I-immunoreactivity patterns appear to be almost exclusively non-overlapping. Very strong cellular retinol-binding protein type I-immunoreactivity is found in the dendritic layers of the hippocampal formation and dentate gyrus. Cellular retinol-binding protein type I-immunoreactivity is also present in layer 5 cortical pyramidal neurons and neurons in the glomerular layer of the olfactory bulb. Many other areas, e.g. hypothalamic nuclei and amygdala areas, contain networks of varicose cellular retinol-binding protein type I-immunoreactive nerve fibers. The medial amygdaloid nucleus contains strongly cellular retinol-binding protein type I-positive neurons. Cellular retinoic acid-binding protein type I-immunoreactivity is more restricted in the adult brain. Strong cellular retinoic acid-binding protein type I-immunore-activity is, however, found in a population of medium-sized neurons scattered throughout the striatum, in neurons in the glomerular layer of the olfactory bulb, the olfactory nerve and in a group of nerve cells close to the third ventricle in hypothalamus. The remarkably selective patterns of cellular retinol-binding protein type I- and cellular retinoic acid-binding protein type I-immunoreactivity discovered in the adult rat brain suggest that retinoids have important roles as regulators of gene expression in normal brain function. The high levels of cellular retinol-binding protein type I-immunoreactivity found in hippocampus suggest that one such role might relate to brain plasticity.