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.