title: Astrocytes as a regulated source of retinoic acid for the brain.
abstract: Retinaldehyde dehydrogenases (RALDH) catalyze the synthesis of the regulatory factor retinoic acid (RA). Cultured astrocytes express several of the RALDH enzyme family, and it has been assumed that this can be extrapolated to astrocytes in vivo. However, this study finds that few astrocytes in the rodent brain express detectable RALDH enzymes, and only when these cells are grown in culture are these enzymes upregulated. Factors controlling the expression of the RALDHs in cultured astrocytes were explored to determine possible reasons for differences between in vitro versus in vivo expression. Retinoids were found to feedback to suppress several of the RALDHs, and physiological levels of retinoids may be one route by which astrocytic RALDHs are maintained at low levels. In the case of RALDH2, in vivo reduction of vitamin A levels in rats resulted in an increase in astrocyte RALDH2 expression in the hippocampus. Other factors though are likely to control RALDH expression. A shift in astrocytic RALDH subcellular localization is a potential mechanism for regulating RA signaling. Under conditions of vitamin A deficiency, RALDH2 protein moved from the cytoplasm to the nucleus where it may synthesize RA at the site of the nuclear RA receptors. Similarly, in conditions of oxidative stress RALDH1 and RALDH2 moved from the cytoplasm to a predominantly nuclear position. Thus, the RALDHs have been revealed to be dynamic in their expression in astrocytes where they may maintain retinoid homeostasis in the brain.
authors.affiliation: Translational Neuroscience, Institute of Medical Sciences, School of Medical Sciences, University of Aberdeen, Aberdeen, Scotland, United Kingdom.
authors.forename: Kirsty D
authors.initials: KD
authors.lastname: Shearer
authors.forename: Yara D
authors.initials: YD
authors.lastname: Fragoso
authors.forename: Margaret
authors.initials: M
authors.lastname: Clagett-Dame
authors.forename: Peter J
authors.initials: PJ
authors.lastname: McCaffery
mesh_terms: D000080924:Aldehyde Dehydrogenase 1 Family; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000378:metabolism / Q000502:physiology*; D001921:Brain / Q000378:metabolism*; D002478:Cells, Cultured; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008875:Middle Aged; D051381:Rats; D017207:Rats, Sprague-Dawley; D050697:Retinal Dehydrogenase / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D014212:Tretinoin / Q000378:metabolism*; D014802:Vitamin A Deficiency / Q000235:genetics / Q000378:metabolism
chemical_list: D014212:Tretinoin; D000080924:Aldehyde Dehydrogenase 1 Family; C545372:ALDH1A2 protein, human; D050697:Retinal Dehydrogenase