(P09-008-25) Fucoxanthin: A Regulator of Mitochondria-Mediated Neuronal Death to Combat Excitotoxicity

Objectives: Mitochondria are the primary intracellular organelles that control neuronal death. During pathological events associated with excitotoxicity, such as cerebral ischemia and neurodegeneration, excess glutamate induces the persistent opening of the mitochondrial permeability transition pore (mPTP). This impairs mitochondrial membrane potential and ATP production leading to neuronal death. Therefore, protecting mitochondria is critical to mitigating excitotoxicity-induced neuronal damage. Fucoxanthin is a carotenoid abundant in brown seaweed that has demonstrated protective effects against neuronal damage in various neurodegeneration models linked to excitotoxicity. We hypothesized that fucoxanthin exerts its protective effects against excitotoxicity by inhibiting mitochondria-mediated death.

Methods: Primary hippocampal neurons isolated from rat fetuses were treated with fucoxanthin (100 nM), glutamate (20 µM), or their combination. Cell death level was determined using propidium iodide (PI) staining. Mitochondrial membrane potential and superoxide anion levels were examined using TMRM and MitoSOX probes, respectively. The opening of the mPTP was assessed using a calcein-cobalt assay. ATP synthase was quantified and visualized using immunoblotting and immunocytochemistry, respectively.

Results: Treatment with fucoxanthin lowered excitotoxicity-induced PI-positive dead cells. In addition, fucoxanthin prevented the loss of TMRM signal and attenuated MitoSOX fluorescence under excitotoxic conditions, suggesting mitochondrial protection. Furthermore, glutamate increased the opening of the mPTP and the dissociation of the ATP synthase subunits, while treatment with fucoxanthin reversed these glutamate effects.

Conclusions: Our findings suggest that fucoxanthin has a protective role in mPTP-associated neuronal death during excitotoxicity. Future investigations elucidating the mechanisms of mitochondrial uptake of fucoxanthin and its interactions with ATP synthase subunits are critical for a comprehensive understanding of the neuroprotective effects of this abundant carotenoid.

Funding Sources: Graduate Council Fellowship, University of Alabama