Retinoic acid is detected at relatively high levels in the CNS of adult rats

Abstract

Retinoic acid (RA) is essential for cellular growth and differentiation in developing and adult animals. The central nervous system (CNS) suffers developmental defects if embryonic levels of RA are too high or too low. The production and function of RA in adult brain are unclear. We report that RA is present throughout the brain and spinal cord of adult, vitamin A-deficient (VAD) rats treated with a physiological amount of all- trans-retinol. The hippocampus/cortex contained the highest proportion of RA in the brain (27.2 ± 2.9% of the organic phase radioactivity, and 23.5 ± 0.8% of the organic phase radioactivity extracted from spinal cord was RA). RA comprises a higher proportion of the retinoid pool in the CNS compared with amounts reported in other target tissues (E Werner and HF DeLuca. Arch Biochem Biophys 393: 262–270, 2001). However, RA is not preferentially transported from the blood to the brain. There were 2.90 ± 0.20 fmol RA/g tissue transported to the brain of VAD rats treated with 2.00 nmol [20-3H]all- trans-retinoic acid, but higher amounts of RA were delivered to the liver, testis, and spleen. Because RA is not transported preferentially to brain, this tissue likely synthesizes RA more efficiently than other target tissues.

Vitamine A et vieillissement cérébral

“…Par la suite, il a ete montre que l'isomere tout-trans de l'AR est la forme la plus largement transportee du sang au cerveau par rapport aux deux autres isoformes, l'AR 13-cis et l'AR 9-cis (Le Doze et al, 2000). Par ailleurs, la presence d'AR a ete mise en evidence au niveau cerebral, chez des rats carences en vitamine A traites avec de l'AR, l'hippocampe et le cortex contenant les proportions les plus importantes (Werner et Deluca, 2002). L'origine de l'AR dans le cerveau semble donc largement exogene dans des situations d'apports suffisants en vitamine A.…”

Evidence for defective retinoid transport and function in late onset Alzheimer's disease

“…RBPs are the major carriers of retinol and titrate the availability of retinol throughout the body (36,59). They are able to carry retinol alone as well as in complex with transthyretin (TTR).…”

“…Retinol is oxidized in two steps, reversibly to retinal by retinol dehydrogenases and then irreveribly by retinaldehyde dehydrogenases to produce the several forms of RA (5). RA is highly efficiently synthesized in the adult hippocampus in rats (59). Degradation of RA, which also controls the level of RA, is initiated by hydroxylation catalyzed by enzymes CYP26A1 and CYP26A2 in the brain (24,65).…”

Detection of Endogenous Retinoids in the Molluscan CNS and Characterization of the Trophic and Tropic Actions of 9-cisRetinoic Acid on Isolated Neurons

“…atRA has been identified in embryonic and adult nervous systems in many vertebrates (Maden et al, 1998b;Hoover et al, 2001;Werner and DeLuca, 2002), but in vivo plasma levels of 9-cis-RA are usually much lower than atRA (Malik et al, 2000) and often fall below detection limits (Kraft and Juchau, 1993). 9-cis-RA has, however, been detected in the neonatal rat eye and human embryonic brain (Kraft and Juchau, 1993) as well as during gastrulation in Xenopus (Kraft et al, 1994).…”