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

Abstract

Background Much attention has recently focused on nutraceuticals which are widely used to promote health. In particular, nutraceuticals with minimal side effects have been 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. Methods To test the neuroprotection of ethanol extract of Aurantiochytrium (EEA) and n-Hex layer of EEA (HEEA), amyloid-beta (Aβ)-stimulated SH-SY5Y cells was used for in vitro AD model. We then assessed the enhancement of neurogenesis of EEA and HEEA using murine ex vivo neurospheres. We also administered EEA or HEEA to SAMP8 mice, a non-transgenic strain with accelerated aging and Alzheimer’s-like memory loss for evaluation of spatial learning and memory using MWM test. Finally, we performed immunohistochemical analysis using mice brain fed with EEA for assessment of neurogenesis. Results Pre-treatment of SH-SY5Y cells with EEA or the squalene-rich fraction of EEA, n-Hex layer (HEEA), ameliorated Aβ-induced cytotoxicity. Interestingly, only EEA-treated cells showed a significant increase in cell metabolism and intracellular ATP production. Moreover, EEA treatment significantly increased the number of neurospheres, whilst 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. Learning ability was assessed in the Morris water maze test. EEA and HEEA decreased escape latency time in SAMP8 mice, indicating improved memory. To detect activated 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 as well as their progeny, BrdU + NeuN + mature neurons. Conclusions Our data in aggregate indicate that EEA and its constituents could be developed into a nutraceutical for promoting brain health and function against some age-related diseases including neurodegenerative desease, particularly AD.

Regulating Early Biological Events in Human Amniotic Epithelial Stem Cells Using Natural Bioactive Compounds: Extendable Multidirectional Research Avenues

“…In hAESCs, isorhamnetin showed anti-fibrotic potential, which was then validated in the cardiac fibrosis in vivo model (Aonuma et al, 2020). The observed neuroprotective potential of microalgaederived squalene (Ferdousi et al, 2021) has also been validated in aging model mice (Sasaki et al, 2019b;Sasaki et al, 2020). Similarly, the chemical synaptic transmission activity of RA was observed in depression model mice (Sasaki et al, 2013;Kondo et al, 2015), and the neurogenesis-regulating effect of TCQA was confirmed in aging mice (Sasaki et al, 2019a).…”