Long-term treatment of fucoxanthin prevents cognitive impairments and neuroinflammation via the inhibition of Nogo-A in APP/PS1 transgenic mice

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by neuroinflammation and cognitive impairments. Although short-term treatment of fucoxanthin, a marine carotenoid with anti-neuroinflammation activity, was reported to prevent cognitive impairments in scopolamine- and β-amyloid (Aβ)-treated mice, it is uncertain whether long-term treatment of fucoxanthin could produce similar effects in transgenic AD animals. Moreover, the anti-neuroinflammation mechanism of fucoxanthin is still unknown. In this study, long-term treatment of fucoxanthin (15-150 mg/kg, twice a week for 20 weeks) significantly prevented cognitive deficits and Aβ-related neuroinflammation in APP/PS1 transgenic mice. In addition, fucoxanthin largely prevented Aβ oligomer-induced secretion of pro-inflammatory cytokines and the activation of BV2 microglial cells. Furthermore, fucoxanthin reduced the increased expression of Nogo-A, a central player for AD pathophysiology, the activation of downstream Rho-associated protein kinase 2 (ROCK2) and nuclear factor kappa-B (NF-κB) pathways in AD models. Most importantly, the inhibition of fucoxanthin on neuroinflammation was not decreased by ShRNA-mediated knockdown of Nogo-A, suggesting fucoxanthin significantly prevented cognitive impairments and neuroinflammation via the inhibition of Nogo-A. These results not only elucidate an anti-neuroinflammation mechanism of fucoxanthin, but also provide a strong support that fucoxanthin could be developed as a novel food ingredient or drug for the treatment of AD.