Microalgae Aurantiochytrium Sp. Increases Neurogenesis and Improves Spatial Learning and Memory in Senescence-Accelerated Mouse-Prone 8 Mice

Abstract

Much attention has recently been focused on nutraceuticals, with minimal adverse effects, developed for preventing or treating neurological diseases such as Alzheimer's disease (AD). The present study was conducted to investigate the potential effect on neural development and function of the microalgae Aurantiochytrium sp. as a nutraceutical. To test neuroprotection by the ethanol extract of Aurantiochytrium (EEA) and a derivative, the n-Hexane layer of EEA (HEEA), amyloid-β-stimulated SH-SY5Y cells, was used as an in vitro AD model. We then assessed the potential enhancement of neurogenesis by EEA and HEEA using murine ex vivo neurospheres. We also administered EEA or HEEA to senescence-accelerated mouse-prone 8 (SAMP8) mice, a non-transgenic strain with accelerated aging and AD-like memory loss for evaluation of spatial learning and memory using the Morris water maze test. Finally, we performed immunohistochemical analysis for assessment of neurogenesis in mice administered EEA. Pretreatment of SH-SY5Y cells with EEA or the squalene-rich fraction of EEA, HEEA, ameliorated amyloid-β-induced cytotoxicity. Interestingly, only EEA-treated cells showed a significant increase in cell metabolism and intracellular adenosine triphosphate production. Moreover, EEA treatment significantly increased the number of neurospheres, whereas HEEA treatment significantly increased the number of β-III-tubulin+ young neurons and GFAP+ astrocytes. SAMP8 mice were given 50 mg/kg EEA or HEEA orally for 30 days. EEA and HEEA decreased escape latency in the Morris water maze in SAMP8 mice, indicating improved memory. To detect stem cells and newborn neurons, we administered BrdU for 9 days and measured BrdU+ cells in the dentate gyrus, a neurogenic stem cell niche of the hippocampus. In SAMP8 mice, EEA rapidly and significantly increased the number of BrdU+GFAP+ stem cells and their progeny, BrdU+NeuN+ mature neurons. In conclusion, our data in aggregate indicate that EEA and its constituents could be developed into a nutraceutical for promoting brain health and function against several age-related diseases, particularly AD.

DNA Microarray-Based Global Gene Expression Profiling in Human Amniotic Epithelial Cells Predicts the Potential of Microalgae-Derived Squalene for the Nervous System and Metabolic Health

“…A neuropeptide NPS increases the excitatory transmitter glutamate secretion and produces anxiolytic-like effects by reducing fear responses [ 49 ]. All these findings align with our previous studies on EEA-SQ that reported antidepressant-like, neuroprotective, and cognition-enhancing effects of EEA-SQ in vivo [ 31 , 32 ].…”

“…The EEA-SQ liquid fraction was concentrated using a SpeedVac (Thermo Fisher Scientific, Japan) and then dissolved in Eagle’s minimum essential serum-free medium through sonication (OPTI-MEM; Gibco, Japan). hAECs were treated with EEA-SQ at a 20 µg/mL concentration following our previous studies [ 31 , 32 ] in human neuroblastoma cells (SHSY5Y cells) and neurospheres of mouse neural progenitor cells. EEA-SQ is safe to use on human cells in general.…”

“…At the University of Tsukuba, a researcher group identified an Aurantiochytrium strain in the Okinawa prefecture of Japan that can accumulate very high SQ (198 mg/g) [ 28 ]. Our previous studies have reported that ethanol extract of Aurantiochytrium 18W-13a (EEA) has anti-inflammatory [ 29 , 30 ], antidepressant-like [ 31 ], and neuroprotective effects [ 32 ]. This SQ rich EEA (EEA-SQ) showed better neuroprotective and neuroproliferative effects compared to SQ only and the n-hexane layer of EEA (squalene-rich fraction) [ 32 ].…”

“…Our previous studies have reported that ethanol extract of Aurantiochytrium 18W-13a (EEA) has anti-inflammatory [ 29 , 30 ], antidepressant-like [ 31 ], and neuroprotective effects [ 32 ]. This SQ rich EEA (EEA-SQ) showed better neuroprotective and neuroproliferative effects compared to SQ only and the n-hexane layer of EEA (squalene-rich fraction) [ 32 ]. The current study aimed to explore the detailed biological functions of EEA-SQ in hAECs using hAEC as a drug screening tool and to identify novel bioactivities of EEA-SQ.…”

Grape skin extract modulates neuronal stem cell proliferation and improves spatial learning in senescence-accelerated prone 8 mice

“…We observed a significant increase in BrdU+ cell numbers in GSE-administered SAMP8 mice. When we prepared the BrdU in water, 1% sucrose was added to induce drinking similar to our previous publications and we consistently observe similar numbers of BrdU+ cells within groups suggesting that drinking behavior and therefore BrdU dose was not altered [ 33 , 48 , 49 ]. It is also formally possible that GSE increased drinking of water, leading to more BrdU+ cells, however there is no a priori reason to believe this was the case.…”