Docosahexaenoic acid improves cognitive function and reduces neuronal apoptosis in an Alzheimer's disease mouse model: association with reduced oxidative stress and telomere attrition.
OBJECTIVE Given the global aging intensification, age-related chronic diseases like Alzheimer's disease (AD) severely harm the elderly's health, with unclear pathogenesis and no effective drugs. Thus, this study intervened in APP/PS1 mice with docosahexaenoic acid (DHA) feeds of different doses to explore DHA's effects on the mice's cognitive function and nerve cell apoptosis, aiming to find the ways to prevent or delay the elderly's cognitive decline. METHODS Six-month-old APP/PS1 mice were divided into 4 groups: wild control (WT), model control (Con), low-dose DHA (DHA-L), and high-dose DHA (DHA-H). After intervention, the study evaluated mice's cognitive function, determined brain AD-related protein and free fatty acid levels, assessed neuronal degeneration and apoptosis, measured telomere oxidative damage, telomere length, and brain oxidative stress levels. RESULTS (1) DHA shortened water maze escape latency, increased platform crossings and target quadrant residence time, and reduced the expression of AD-related proteins (APP, Aβ, etc.) (P < 0.05); (2) It improved brain neuronal degeneration and apoptosis (P < 0.05); (3) It enhanced brain antioxidant capacity, regulated SOD, LPO, and MDA levels, and reduced DNA and telomere oxidative damage (P < 0.05); (4) It prolonged brain telomere length (P < 0.05). CONCLUSION DHA supplementation can improve cognitive decline in AD model mice, and the mechanism may be that DHA supplementation alleviates oxidative stress-mediated telomere wear in brain tissue, thereby inhibiting apoptosis of neuronal cells. These conditions provide a scientific basis for the elderly and people with cognitive impairment to prevent or alleviate cognitive impairment with reasonable intake of DHA.