Fucoidan inhibits cellular and neurotoxic effects of β‐amyloid (Aβ) in rat cholinergic basal forebrain neurons

The deposition of β‐amyloid protein (Aβ), a 39–43 amino acid peptide, in the brain and a loss of cholinergic neurons in the basal forebrain are pathological hallmarks of Alzheimer's disease (AD). Seaweeds consumed in Asia contain Fucoidan, a sulfated polysaccharide. Fucoidan has been known to exhibit various biological actions, such as an anti‐inflammatory and antioxidant action. In this study, using whole‐cell patch clamp recordings we examined the effects of Fucoidan on Aβ‐induced whole‐cell currents in acutely dissociated rat basal forebrain neurons. We further investigated whether Fucoidan is capable of blocking Aβ neurotoxicity in primary neuronal cultures. In dissociated cells, bath application of Aβ 25−35 (1 µ m ) caused a reduction of the whole‐cell currents by 16%. Fucoidan, in a dose‐dependent manner, blocks the Aβ 25−35 reduction of whole‐cell currents. Exposure of Aβ 25−35 (20 µ m ) or Aβ 1−42 (20 µ m ) to rat cholinergic basal forebrain cultures for 48 h resulted in 40–60% neuronal death, which was significantly decreased by pretreatment of cultures with Fucoidan (0.1–1.0 µ m ). Fucoidan also attenuated Aβ‐induced down‐regulation of phosphorylated protein kinase C. Aβ 1−42 ‐induced generation of reactive oxygen species was blocked by prior exposure of cultures to Fucoidan. Furthermore, Aβ activation of caspases 9 and 3, which are signaling pathways implicated in apoptotic cell death, is blocked by pretreatment of cultures with Fucoidan. These results show that Fucoidan is able to block Aβ‐induced reduction in whole‐cell currents in basal forebrain neurons and has neuroprotective effects against Aβ‐induced neurotoxicity in basal forebrain neuronal cultures.