@article{Bie2026, 
author = {Nana Bie and Mengdi Yan and Chunling Wang},
title = {Docosahexaenoic acid improves synaptic structure and function in APP/PS1 mice through the TrkB-Erk1/2-CREB pathway},
year = {2026},
journal = {Food Science and Human Wellness},
volume = {15},
number = {2},
pages = {9250517},
keywords = {Docosahexaenoic acid, Alzheimer’s disease, Amyloid-beta, Synapse},
url = {https://www.sciopen.com/article/10.26599/FSHW.2025.9250517},
doi = {10.26599/FSHW.2025.9250517},
abstract = {Alzheimer’s disease (AD) is a serious disease associated with cognitive impairment, and synaptic loss and amyloid-beta (Aβ) deposition are closely related to its pathogenesis. Docosahexaenoic acid (DHA) has been reported to alter the cognitive impairment associated with aging and reduce the risk of long-term development of AD. However, the effects of Aβ on synapses and whether DHA has a protective effect on synapses remain unclear. In this study, APPSwe/PSEN1dE9 transgenic and wild type mice were used as experimental subjects to explore the effect of DHA on synaptic structure and function damaged by Aβ. Results showed that a large amount of Aβ was deposited in the brain of AD mice, and DHA intervention decreased the Aβ deposition (P < 0.05). DHA decreased the apoptosis of nerve cells and the oxidative stress level induced by Aβ (P < 0.01). Transmission electron microscopy results showed that DHA improved the synaptic structure and number, and the expression of synaptophysin was significantly upregulated by DHA (P < 0.01). Besides, neurotransmitter release was regulated after DHA intervention, including the decreased Glu level and increased γ-aminobutyric acid level, as well as the activity of ATPase was also increased by DHA. Importantly, the phosphorylation levels of tyrosine kinase B (TrkB), phospholipase C-gamma-1, calcium/calmodulin-dependent protein kinase Ⅱ, extracellular regulated protein kinases (ERK1/2), and cAMP-response element binding protein (CREB) were upregulated by DHA (P < 0.01). These data indicated that DHA could improve synaptic structure and function through the TrkB-Erk1/2-CREB pathway, thus playing a positive role in the pathological process of AD.}
}