Retinoic acid normalizes nuclear receptor mediated hypo-expression of proteins involved in beta-amyloid deposits in the cerebral cortex of vitamin A deprived rats.
Recent data have revealed that disruption of vitamin A signaling observed in Alzheimer's disease (AD) leads to a deposition of beta-amyloid (Abeta). The aim of this study was to precise the role of vitamin A and its nuclear receptors (RAR) in the processes leading to the Abeta deposits. Thus, the effect of vitamin A depletion and subsequent administration of retinoic acid (RA, the active metabolite of vitamin A) on the expression of RARbeta, and of proteins involved in amyloidogenic pathway, e.g., amyloid precursor protein (APP), beta-secretase enzyme (BACE), and APP carboxy-terminal fragment (APP-CTF) was examined in the whole brain, hippocampus, striatum, and cerebral cortex of rats. Rats fed a vitamin A-deprived diet for 13 weeks exhibited decreased amount of RARbeta, APP695, BACE, and of APP-CTF in the whole brain and in the cerebral cortex. Administration of RA is able to restore all expression. The results suggest that fine regulation of vitamin A mediated gene expression seems fundamental for the regulation of APP processing.
Unité de Nutrition et Signalisation Cellulaire (E.A. MENRT; USC INRA) ISTAB, Université Bordeaux 1, Avenue des Facultés, 33405 Talence cedex, France.
Marianne
M
Husson
Valérie
V
Enderlin
André
A
Delacourte
Nadirah
N
Ghenimi
Serge
S
Alfos
Véronique
V
Pallet
Paul
P
Higueret
D053829:Amyloid Precursor Protein Secretases; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D016282:Aspartic Acid Endopeptidases; D015153:Blotting, Western; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010450:Endopeptidases / Q000187:drug effects / Q000378:metabolism; D008297:Male; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D018168:Receptors, Retinoic Acid / Q000187:drug effects* / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology*; D014801:Vitamin A / Q000378:metabolism; D014802:Vitamin A Deficiency / Q000503:physiopathology*
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid; D014801:Vitamin A; D014212:Tretinoin; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases; D016282:Aspartic Acid Endopeptidases; C509281:Bace1 protein, rat