Inhibition Of Astaxanthin On A-beta-induced Toxicity In AD Mouse Model And Its Protective Mechanisms

Alzheimer’s disease(AD)is a neurodegenerative disease that causes high morbidity in older people.Although the pathogenic mechanism of AD is still inconclusive,Aβ has been widely recognized to play an important role in AD.For understanding the inhibitory mechanisms of astaxanthin(AST)on the toxicity of Aβ,APPswe/PS1 d E9(APP/PS1)mice were orally administrated with AST for 3 month.Congo red staining showed that AST significantly decreased the area of Aβ plaque in the brain of APP/PS1 mice.Analyzing the levels of amyloid precursor protein(APP),Aβ monomer and oligomers and BACE1 with Western blot showed that AST reduced the toxicity of Aβ via inhibiting the production of oligomers.TUNEL staining showed that AST decreased the apoptosis in the brain of APP/PS1 mice.The results also showed AST significantly reduced the activation of caspase-3and the ratio of Bax/Bcl-2 in the brain of APP/PS1 mice,and significantly evelated the activation of Akt and the phosphorylation of Bad.Improved Bielschowsky sliver staining showed that AST significantly decreased the production of neurofibrillary tangles(NFTs)that are mainly composed of hyperphosphorylated tau proteins.Western blot showed that AST reduced hyperphosphorylated tau via decreasing the activation of p38 mitogen activated protein kinase(MAPK).Malondialdehyde(MDA),a marker of lipid peroxidation,was decreased by AST in the brain of APP/PS1 mice.Overall,AST may reduce the toxicity of Aβ by reducing Aβaccumulation,neuronal apoptosis,tau phosphorylation and oxidative stress.