Ameliorating Activity of Ishige okamurae on the Amyloid Beta-Induced Cognitive Deficits and Neurotoxicity through Regulating ERK, p38 MAPK, and JNK Signaling in Alzheimer's Disease-Like Mice Model

Scope Alzheimer's disease (AD) is associated with amyloid beta peptide (A beta(25-35)) accumulation in brains, which induces neurotoxicity and cognitive impairment. The effects of Ishige okamurae, an edible brown algae, on A beta(25-35)-induced cognitive impairment and neuronal toxicity is investigated. The aim of this study is to determine the molecular mechanisms responsible for I. okamurae extracts (IOE) mediating anti-AD effects. Methods and Results Oral administration of IOE significantly attenuated A beta(25-35)-induced cognitive deficits, as estimated by Y-maze and Morris water maze tests. IOE also attenuated the A beta(25-35)-induced cellular apoptosis and expression of inducible isoforms of nitric oxide synthases (iNOS) and cyclooxygenase-2 (COX-2) in mouse brains and PC12 cells. In addition, A beta(25-35)-induced phosphorylation of ERK, p38 MAPK, and JNK in mouse brains and PC12 cells is significantly abolished by administration of IOE. In PC12 cells, pretreatment of signal inhibitors (PD98059 (MEK inhibitor), SB203580 (p38 MAPK inhibitor), and SP600125 (JNK inhibitor)) recovers A beta(25-35)-mediated cellular dysregulations to the same extent as does IOE pretreatment. Conclusion Taken together, the data suggest that A beta(25-35)-induced AD progress may be attenuated by administration of IOE through prevention of A beta(25-35)-induced phosphorylation of ERK, p38 MAPK, and JNK.