DHA COMBINED WITH MCTS ALLEVIATES NEURONAL DAMAGE IN SAMP8 MICE VIA MTOR/TFEB-MEDIATED AUTOPHAGY-LYSOSOMAL PATHWAY

GUO Shuang-shuang; WANG Ze-hao; HE Xin; LI Wen; HUANG Guo-wei; LI Zhen-shu

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Acta Nutrimenta Sinica ›› 2025, Vol. 47 ›› Issue (6) : 569-580.

ORIGINAL ARTICLES

DHA COMBINED WITH MCTS ALLEVIATES NEURONAL DAMAGE IN SAMP8 MICE VIA MTOR/TFEB-MEDIATED AUTOPHAGY-LYSOSOMAL PATHWAY

GUO Shuang-shuang¹, WANG Ze-hao¹, HE Xin¹, LI Wen^1,2,3, HUANG Guo-wei^1,2,3, LI Zhen-shu^1,2,3

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Abstract

Objective To investigate the effects of docosahexaenoic acid (DHA) combined with medium chain triglycerides (MCTs) on neuronal damage in senescence-accelerated mouse prone 8 (SAMP8) mice and the potential autophagy-lysosomal pathway mechanism. Methods 4-month-old SAMP8 mice were randomly assigned to four groups: 0.233% DHA supplementation (DHA group), 10% MCTs supplementation (MCTs group), 0.233% DHA+10% MCTs supplementation (DHA+MCTs group), and control (Con-P group). Four-month-old senescence-accelerated mouse resistant 1 (SAMR1) mice served as the normal aging control group (Con-R group). After 7 months of dietary intervention, brain tissue sections were prepared. Fluoro-Jade B (FJB) staining was used to assess neuronal degeneration in the cerebral cortex. Nissl staining was conducted to quantify surviving neurons. Immunofluorescence was employed to assess expression levels of autophagy-related and lysosome-related proteins. Results FJB staining revealed that compared to the Con-P group, the DHA, MCTs, and DHA+MCTs groups exhibited reduced numbers of degenerated neurons, while the DHA+MCTs group demonstrated the lowest number of degenerated neurons compared to the DHA and MCTs groups, and these differences were all statistically significant (P<0.05). Nissl staining revealed that the number of surviving neurons in the DHA, MCTs, and DHA+MCTs groups was higher than in the Con-P group. The DHA+MCTs group exhibited the highest number of surviving neurons (P<0.05). Immunofluorescence results showed that compared to the Con-P group, mTOR expression levels were higher in the DHA, MCTs, and DHA+MCTs groups (P<0.05). Furthermore, mTOR expression in the DHA+MCTs group was higher than in the DHA and MCTs groups. Meanwhile, expression levels of the key regulatory proteins for autophagy and lysosomal function (TFEB), the autophagy-related proteins (LC3 and Beclin-1) and the lysosomal-associated proteins (LAMP1, LAMP2, CTSB and CTSD) were all significantly reduced (P<0.05). Conclusion DHA combined with MCTs alleviates neuronal damage in the cerebral cortex of SAMP8 mice and the combined supplementation yields superior effects compared to either DHA or MCTs alone. The mechanism is related to the regulation of the mTOR/TFEB-mediated autophagy-lysosomal pathway.

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docosahexaenoic acid / medium chain triglycerides / autophagy-lysosomal pathway / neuron / SAMP8 mice

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GUO Shuang-shuang, WANG Ze-hao, HE Xin, LI Wen, HUANG Guo-wei, LI Zhen-shu. DHA COMBINED WITH MCTS ALLEVIATES NEURONAL DAMAGE IN SAMP8 MICE VIA MTOR/TFEB-MEDIATED AUTOPHAGY-LYSOSOMAL PATHWAY[J]. Acta Nutrimenta Sinica. 2025, 47(6): 569-580

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