Prophylactic Effect of All-Trans Retinoic Acid in An Amyloid-Beta Rat Model of Alzheimer’S Disease

Introduction: retinoid signaling has been argued to have favorable effects on alzheimer’s disease (ad). we studied the role of chronic intracerebroventricular (icv) injection of all-trans retinoic acid (atra) on the amyloid-beta (aβ) model of ad. methods: adult male rats weighing 260-330 g were divided into 12 groups of 8 each. six groups of rats received atra (3nm,30nm,3μm,0.3mm,30mm/rat; icv) or dmso 1% (2μl/rat; icv),bilaterally and in a chronic manner (6 times,twice a week). forty eight hours following the last injection,memory performance was assessed using a passive avoidance paradigm. one group received aβ (10μg/rat; icv),bilaterally. the control group received dmso 1% (2μl/rat; icv). twenty days later memory performance was assessed. three groups of rats received aβ (10μg/rat; icv) and then atra (3nm or 30nm/rat; icv) or dmso 1%,chronically (6 times,twice a week). another group received dmso 1% (2μl/rat; icv) and then,dmso 1%,chronically (6 times,twice a week). results: atra at doses 0.3mm and 30mm/rat impaired memory retrieval by decreasing step-through latency (stl) and increasing time spent in the dark compartment (tdc),significantly. however,moderate doses (3nm and 30nm/rat) did not change memory performance. atra (30nm/rat) increased stl and decreased tdc and nst in the aβ-treated rats,significantly compared to the group received aβ- dmso 1%. conclusion: the results propose a potential prophylactic effect of atra in the icv aβ model of ad and indicate the prominence of retinoic acid signaling as a target for ad prevention. © 2017,iranian society of physiology and pharmacology. all rights reserved.