Simultaneous intake of chlorella and ascidian ethanolamine plasmalogen accelerates activation of BDNF-TrkB-CREB signaling in rats.

Simultaneous intake of chlorella and ascidian ethanolamine plasmalogen accelerates activation of BDNF-TrkB-CREB signalling in rats.

Takekoshi H, Fujishima M, Miyazawa T, Higuchi O, Fujikawa T, and Miyazawa T. (2024) Simultaneous intake of chlorella and ascidian ethanolamine plasmalogen accelerates activation of BDNF-TrkB-CREB signaling in rats. Molecules, 29, 357

Alzheimer’s disease (AD) is a progressive neurodegenerative disease characterized by memory loss and cognitive decline. Although many factors have been found to be associated with an increased risk for AD, one consistent cause has not been identified. One of these factors is a reduction in brain-derived neurotrophic factor (BDNF), a neurotrophin that is important for neurogenesis, synaptic plasticity, and cognition through binding to tropomyosin receptor kinase b (TrkB). This leads to TrkB autophosphorylation and the activation of molecules such as cAMP response element-binding protein (CREB) (BDNF-TrkB-CREB signaling pathway). Interestingly, certain foods or ingredients are able to increase BDNF expression including plasmalogens and lutein (xanthophylls or an oxygen-rich carotenoid). Plasmalogens are a class of phospholipid that contain a vinyl-ether bond at the sn-1 position of the glycerol backbone and are a large component of the brain. In addition, they are important to the structure and function of cellular membranes, are required for vesicular fusion, and have antioxidative properties. The authors had previously performed a study using Chlorella pyrenoidosa powder supplementation to provide lutein in older adults to reduce phospholipid hydroperoxide and maintain erythrocyte function. In addition, previous work supplementing with ascidian-derived plasmalogens demonstrated an ability to supress neuroblast apoptosis, improve cognitive function, and prevent beta-amyloid aggregation in in vivo and in vitro studies. Because of this, Takekoshi et al wanted to determine if a combined supplementation of lutein-rich Chlorella and plasmalogens extracted from ascidian (Halocynthia roretzi) could influence the BDNF-TrkB-CREB signaling pathway in the hippocampus of Sprague-Dawley rats.

To determine the effect of combining plasmalogen supplementation with lutein supplementation, rats were separated into four different treatment groups each consisting of five rats: controls (CON) which received a vehicle of soybean oil/canola oil and normal diet; Chlorella (CHL) which received soybean oil/canola oil and a diet containing Chlorella; ascidian extract (HRE) which received ascidian extract and a normal diet; or Chlorella + ascidian extract (CHL + HRE) which received ascidian extract and a diet containing Chlorella. Chlorella was dosed at 200 mg/day/rat and ascidian extract was dosed at 0.07 mg/day/rat of ethanolamine plasmalogen. The animals were dosed daily for one week then western blots were performed using hippocampal tissue to analyze protein expression and phosphorylation of proteins associated with BDNF signaling. They looked at BDNF, phosphorylated TrkB, and phosphorylated CREB and found that consistently the combined supplementation in CHL + HRE group had increased expression compared to the groups supplemented with either ethanolamine plasmalogens or lutein. As well, phosphorylated TrkB and phosphorylated CREB were increased to levels significantly greater than the controls. In this study, neither ethanolamine plasmalogens or lutein was able to significantly change the expression of any of the three target proteins, suggesting that together there was a synergistic effect caused by the dual supplementation.

After seeing success in previous studies, Takekoshi et al were interested in determining if a combined administration of lutein-rich Chlorella and ascidian-derived ethanolamine plasmalogens would have an increased effect on the BDNF-TrkB-CREB pathway compared to either supplementation route alone. Interestingly, they found no difference in either the CHL or the HRE groups compared to control, but the CHL + HRE group had significantly increased expression of BDNF, phosphorylated TrkB, and phosphorylated CREB compared to either individual administration. As well, this group showed significantly increased expression in phosphorylated TrkB and phosphorylated CREB compared to the control group. One limitation of these findings is that the study was only run for one week and although the results do demonstrate that the combination of ethanolamine plasmalogens and lutein enhanced activation of the BDNF-TrkB-CREB signaling pathway, further work in longer studies is necessary. The authors state that the studies this work was based on showed an effect of either treatment, however the study designs were not the same as performed here. In both cases, the previous studies were run for much longer periods of time and the Chlorella study was performed in humans, which may explain the differences seen in this study. Additional research using animal models of AD or dementia could also indicate if these changes in protein expression elicit clinically relevant improvements to the disease.