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.

Abstract

Alzheimer's disease (AD) is associated with amyloid beta peptide (Aβ25-35 ) accumulation in brains, which induces neurotoxicity and cognitive impairment. The effects of Ishige okamurae, an edible brown algae, on Aβ25-35 -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. Oral administration of IOE significantly attenuated Aβ25-35 -induced cognitive deficits, as estimated by Y-maze and Morris water maze tests. IOE also attenuated the Aβ25-35 -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, Aβ25-35 -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 Aβ25-35 -mediated cellular dysregulations to the same extent as does IOE pretreatment. Taken together, the data suggest that Aβ25-35 -induced AD progress may be attenuated by administration of IOE through prevention of Aβ25-35 -induced phosphorylation of ERK, p38 MAPK, and JNK.