Inhibitory effects of long-term administration of ferulic acid on astrocyte activation induced by intracerebroventricular injection of beta-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 (Abeta)1-42 in mice. In that report, we found that the Abeta1-42-induced increases in immunoreactivities of glial fibrillary acidic protein, the astrocyte marker, and interleukin(IL)-1beta in the hippocampus 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 Abeta1-42-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 Abeta1-42 (410 pmol) was administered via intracerebroventricular injection. Intracerebroventricularly injected Abeta1-42 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 Abeta1-42-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 Abeta1-42 also increased interleukin-1alpha(IL-1alpha) 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 centrallly injected Abeta1-42-induced activation of astrocytes which is suggested to underlie the protective effect of ferulic acid against Abeta1-42 toxicity in vivo.
Cho
Jae-Young
JY
Department of Pharmacology, College of Medicine, Institute of Natural Medicine, Hallym University, Chunchon, 200-702, South Korea.
Kim
Hee-Sung
HS
Kim
Do-Hoon
DH
Yan
Ji-Jing
JJ
Suh
Hong-Won
HW
Song
Dong-Keun
DK
D016229:Amyloid beta-Peptides / Q000008:administration & dosage* / Q000037:antagonists & inhibitors; D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D003373:Coumaric Acids / Q000008:administration & dosage*; D004347:Drug Interactions; D016166:Free Radical Scavengers / Q000008:administration & dosage*; D005786:Gene Expression Regulation / Q000187:drug effects; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects; D007150:Immunohistochemistry / Q000379:methods; D007276:Injections, Intraventricular / Q000379:methods; D007375:Interleukin-1 / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000037:antagonists & inhibitors; D013997:Time Factors; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D016229:Amyloid beta-Peptides; D003373:Coumaric Acids; D016166:Free Radical Scavengers; D005904:Glial Fibrillary Acidic Protein; D007375:Interleukin-1; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); C002744:3-nitrotyrosine; D014443:Tyrosine; C004999:ferulic acid; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse