Protection against beta-amyloid peptide toxicity in vivo with long-term administration of ferulic acid

1 beta -Amyloid peptide (A beta), a 39-43 amino acid peptide, is believed t o induce oxidative stress and inflammation in the brain, which are postulat ed to play important roles in the pathogenesis of Alzheimer's disease. Feru lic acid is an antioxidant and anti-inflammatory agent derived from plants; therefore, the potential protective activity of ferulic acid against A bet a toxicity in vivo was examined. 2 Mice were allowed free access to drinking water (control) or water contai ning ferulic acid (0.006%). After 4 weeks, A beta1-42 (410 pmol) was admini stered vh intracerebroventricular injection. 3 Injection of control mice with A beta1-42 impaired performance on the pas sive avoidance test (35% decrease in step-through latency), the Y-maze test (19% decrease in alternation behaviour), and the water maze test (32% decr ease in percentage time in platform-quadrant). In contrast, mice treated wi th ferulic acid prior to A beta1-42 administration were protected from thes e changes (9% decrease in step-through latency; no decrease in alternation behaviour; 14% decrease in percentage time in platform-quadrant). A beta1-4 2 induced 31% decrease in acetylcholine level in the cortex, which was tend ed to be ameliorated by ferulic acid. 4 In addition, A beta1-42 increased immunoreactivities of the astrocyte mar ker glial fibrillary acidic protein (GFAP) and interleukin-1 beta (IL-1 bet a) in the hippocampus, effects also suppressed by pretreatment with ferulic acid. 5 Administration of ferulic acid pet sc unexpectedly induced a transient an d slight increase in GFAP and IL-1 beta immunoreactivity in the hippocampus on day 14, which returned to basal levels on day 28. A slight (8%) decreas e in alternation behaviour was observed on day 14. 6 These results demonstrate that long-term administration of ferulic acid i nduces resistance to A beta1-42 toxicity in the blain, and suggest that fer ulic acid may be a useful chemopreventive agent against Alzheimer's disease .