(P25-015-24) Is Fucoxanthin a Potential Regulator of the Mitochondrial Permeability Transition Pore?

Objectives: =Excitotoxicity is a condition that is observed during brain disorders such as cerebral ischemia and is a result of an excessive release of glutamate in the brain. During excitotoxicity, cytosolic calcium overload triggers the opening of the mitochondrial permeability transition pore (mPTP), which disrupts the integrity of the mitochondrial membrane and causes energy depletion, ultimately leading to neuronal death. Fucoxanthin is a carotenoid found in brown seaweed that protects the brain against the pathology associated with mitochondrial dysfunction. However, the cellular mechanisms of fucoxanthin-mediated neuroprotection have yet to be elucidated. The objective of this study was to investigate the potential role of fucoxanthin in the regulation of mPTP in an in vitro model of excitotoxicity.

Methods: Rat primary hippocampal neurons were treated with 100 nM of fucoxanthin, 20 μM of glutamate, or a combination of both. Cell viability was determined by Calcein and propidium iodide (PI) staining, and mitochondrial membrane potential and superoxide level were assessed using tetramethylrhodamine methyl ester (TMRM) and MitoSOX staining, respectively.

Results: Glutamate exposure resulted in a decrease in the calcein signal and an increase in PI-positive cells, indicating increased cell death, whereas treatment with fucoxanthin prevented glutamate-induced cell death. In addition, fucoxanthin prevented the glutamate-induced loss of mitochondrial membrane potential and mitochondrial superoxide production.

Conclusions: This study showed that fucoxanthin prevented neuronal death from excitotoxicity through mitochondrial protection. Further research investigating the molecular target of fucoxanthin should be conducted to elucidate the mechanisms of fucoxanthin in the regulation of mPTP.

Funding Sources: Graduate Council Fellowship, University of Alabama