Effects of dihydroartemisinin on cognitive behavior, β-amyloid and autophagy proteins in brain and retina of 5×FAD mice

doi:10.16098/j.issn.0529-1356.2025.03.003

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Acta Anatomica Sinica ›› 2025, Vol. 56 ›› Issue (3) : 270-276. DOI: 10.16098/j.issn.0529-1356.2025.03.003

Neurobiology

Effects of dihydroartemisinin on cognitive behavior, β-amyloid and autophagy proteins in brain and retina of 5×FAD mice

HOU Yi-wei¹ YANG Yu² WANG Zhi-xin¹ YI Li³ ZHOU Hang¹ LI Bei-han¹ YAO Hong-bo^1* GAO Han³ WANG Yu-chun⁴ ZHANG Ke-shuang¹

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Abstract

Objective To explore the pathogenesis of Alzheimer’s disease by examining the effects of dihydroartemisinin(DHA) on cognitive behavior, hippocampal, cerebral cortex and retinal cell morphology, β-amyloid(Aβ) and autophagy-related proteins in 5×FAD mice. Methods Twenty 5×FAD mice and 5 wild type (WT) mice were selected, all of which were female. The 5×FAD mice were randomly divided into model (M) group, donepezil (D) group, low-dose DHA (DHA-L) group, and high-dose DHA (DHA-H) group. The WT and M groups were not treated, and the D group was given donepezil 0.1 mg/kg per day. DHA-L group and DHA-H group were given 10 mg/kg and 20 mg/kg DHA per day, respectively. Group D, group DHA-L and group DHA-H were given intragastric administration once a day for 3 months. The changes of in cognitive behavior were measured by Morris experiment. HE staining was used to observe the arrangement and morphology of nerve cells in cerebral cortex, hippocampus and retina. The expressions of Aβ protein in cerebral cortex, hippocampus and retina were detected by immunohistochemistry. Western blotting detected the expression of autophagy related proteins (LC3-Ⅰ, LC3-Ⅱ, Beclin-1, P62, β-actin). Results The DHA-H group and the D group exhibited more frequent adoption of both linear and trending exploration routes. Compared to the model group, significant differences in the contents of Aβ in the hippocampal CA1, cerebral cortex S1, and retinal were observed (P<0.0001) in the other four groups. The analysis also showed significant differences in autophagy-associated proteins between the DHA-L, DHA-H, and model groups (P<0.01). Conclusion DHA improves cognitive function and increases the number of nerve cells in mice. It also reduces Aβ content in the cerebral cortex, hippocampus, and retina, along with improving autophagy-associated protein deposition in mice.

Key words

Alzheimer’s disease / Age-related macular degeneration / Dihydroartemisinin / Autophagy / Western blotting / Mouse

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HOU Yi-wei YANG Yu WANG Zhi-xin YI Li ZHOU Hang LI Bei-han YAO Hong-bo GAO Han WANG Yu-chun ZHANG Ke-shuang. Effects of dihydroartemisinin on cognitive behavior, β-amyloid and autophagy proteins in brain and retina of 5×FAD mice[J]. Acta Anatomica Sinica. 2025, 56(3): 270-276 https://doi.org/10.16098/j.issn.0529-1356.2025.03.003

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