Differential effect of retinoic acid and triiodothyronine on the age-related hypo-expression of neurogranin in rat.
Given the important role of retinoids and thyroid hormone for optimal brain functioning and the tenuous relationship between retinoic acid (RA) and triiodothyronine (T3) signalings, we compared the effects of RA or T3 administrations on RA and T3 nuclear receptors (RAR, RXR and TR) and on their target genes, neuromodulin (GAP43) and neurogranin (RC3) in 24-month-old rats. Quantitative real time PCR and western blot analysis allowed us to verify that retinoid and thyroid signalings and GAP43 and RC3 expression are affected by age. By in situ hybridization we observed a decreased expression of RC3 in hippocampus, striatum and cerebral cortex. RARbeta, RXRbeta/gamma and GAP43 were up-regulated by RA as well as T3 treatment. The abundance of TRalpha/beta mRNA and RC3 expression were only increased by T3 administration in the whole brain. This up-regulator effect of T3 on RC3 was only observed in the striatum. During aging, T3 become a limiting factor alone able to correct the age-related concomitant hypo-activation of retinoid and thyroid signalings and alterations of synaptic plasticity.
Féart
C
C
Unité de Nutrition et Signalisation Cellulaire (E.A. MENRT; USC INRA) ISTAB, Avenue des Facultés, Université Bordeaux I, 33405 Talence cedex, France.
Mingaud
F
F
Enderlin
V
V
Husson
M
M
Alfos
S
S
Higueret
P
P
Pallet
V
V
D000375:Aging / Q000502:physiology*; D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western / Q000379:methods; D001921:Brain / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism; D002148:Calmodulin-Binding Proteins / Q000378:metabolism*; D019922:GAP-43 Protein / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D017403:In Situ Hybridization / Q000379:methods; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D051579:Neurogranin; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D014212:Tretinoin / Q000097:blood / Q000494:pharmacology*; D014284:Triiodothyronine / Q000097:blood / Q000494:pharmacology*
D002148:Calmodulin-Binding Proteins; D019922:GAP-43 Protein; D009419:Nerve Tissue Proteins; C496651:Nrgn protein, rat; D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid; C082925:retinoic acid receptor beta; D014284:Triiodothyronine; D051579:Neurogranin; D014212:Tretinoin