Inhibitory effects of long-term administration of ferulic acid on astrocyte activation induced by intracerebroventricular injection of β-amyloid peptide (1-42) in mice

Accumulating evidence indicates that glial cells are actively involved in the pathogenesis of Alzheimer's disease. We recently reported protective effects of long-term administration of ferulic acid against learning and memory deficit induced by centrally administered beta-amyloid peptide (A beta)1-42 in mice. In that report, we found that the A beta 1-42-induced increases in immunoreactivities of glial fibrillary acidic protein, the astrocyte marker, and interleukin-1 beta in the bippocampus are also suppressed by pretreatment with ferulic acid. In the present study, we aimed to further characterize the effect of long-term administration of ferulic acid on the centrally administered A beta 1-42-induced activation of glial cells in mice. Mice were allowed free access to drinking water (control) or water containing ferulic acid (0.006%) for 4 weeks, and then A beta 1-42 (410 pmol) was administered via intracerebroventricular injection. Intracerebroventricularly injected A beta 1-42 induced an increase in immunoreactivities of endothelial nitric oxide synthase (eNOS) and 3-nitrotyrosine (3-NT) in the activated astrocytes in the hippocampus. Pretreatment of ferulic acid for 4 weeks prevented the A beta 1-42-induced increase in eNOS and 3-NT immunoreactivities. Administration of ferulic acid per se induced a transient and slight increase in eNOS immunoreactivity in the hippocampus on day 14, which returned to basal levels on day 28. Intracerebroventricularly injected A beta 1-42 also increased interleukin-1 alpha(IL-1 alpha) immunoreactivity in the hippocampus, which was also suppressed by pretreatment with ferulic acid. These results demonstrate that long-term administration of ferulic acid induces suppression of the centrality injected A beta 1-42-induced activation of astrocytes which is suggested to underlie the protective effect of ferulic acid against A beta 1-42 toxicity in vivo. (c) 2005 Elsevier Inc. All rights reserved.