Protective effect of scallop-derived plasmalogen against vascular dysfunction, via the pSTAT3/PIM1/NFATc1 axis, in a novel mouse model of Alzheimer's disease with cerebral hypoperfusion.

A strong relationship between Alzheimer's disease (AD) and vascular dysfunction has been the focus of increasing attention in aging societies. In the present study, we examined the long-term effect of scallop-derived plasmalogen (sPlas) on vascular remodeling-related proteins in the brain of an AD with cerebral hypoperfusion (HP) mouse model. We demonstrated, for the first time, that cerebral HP activated the axis of the receptor for advanced glycation endproducts (RAGE)/phosphorylated signal transducer and activator of transcription 3 (pSTAT3)/provirus integration site for Moloney murine leukemia virus 1 (PIM1)/nuclear factor of activated T cells 1 (NFATc1), accounting for such cerebral vascular remodeling. Moreover, we also found that cerebral HP accelerated pSTAT3-mediated astrogliosis and activation of the nucleotide-binding domain and leucine-rich repeat protein 3 (NLRP3) inflammasome, probably leading to cognitive decline. On the other hand, sPlas treatment attenuated the activation of the pSTAT3/PIM1/NFATc1 axis independent of RAGE and significantly suppressed NLRP3 inflammasome activation, demonstrating the beneficial effect on AD.

Inhibitory Effect of Adsorption of Streptococcus mutans onto Scallop-Derived Hydroxyapatite.

Hydroxyapatite adsorbs various substances, but little is known about the effects on oral bacteria of adsorption onto hydroxyapatite derived from scallop shells. In the present study, we analyzed the effects of adsorption of Streptococcus mutans onto scallop-derived hydroxyapatite. When scallop-derived hydroxyapatite was mixed with S. mutans, a high proportion of the bacterial cells adsorbed onto the hydroxyapatite in a time-dependent manner. An RNA sequencing analysis of S. mutans adsorbed onto hydroxyapatite showed that the upregulation of genes resulted in abnormalities in pathways involved in glycogen and histidine metabolism and biosynthesis compared with cells in the absence of hydroxyapatite. S. mutans adsorbed onto hydroxyapatite was not killed, but the growth of the bacteria was inhibited. Electron microscopy showed morphological changes in S. mutans cells adsorbed onto hydroxyapatite. Our results suggest that hydroxyapatite derived from scallop shells showed a high adsorption ability for S. mutans. This hydroxyapatite also caused changes in gene expression related to the metabolic and biosynthetic processes, including the glycogen and histidine of S. mutans, which may result in a morphological change in the surface layer and the inhibition of the growth of the bacteria.

Orally Administered Plasmalogens Alleviate Negative Mood States and Enhance Mental Concentration: A Randomized, Double-Blind, Placebo-Controlled Trial.

Background: Plasmalogens have been shown to improve neurodegenerative pathology and cognitive function. We hypothesized that plasmalogens work in small amounts as a kind of hormone interacting with a G protein-coupled receptor, and then explored the effects of scallop-derived purified plasmalogens on psychobehavioral conditions in a randomized placebo-controlled trial of college athletes in Japan. Methods and materials: Eligible participants were male students aged 18-22 years who belonged to university athletic clubs. They were randomly allocated to either plasmalogen (2 mg per day) or placebo treatment of 4 weeks' duration. The primary outcome was the T-score of the Profile of Mood States (POMS) 2-Adult Short, and the secondary outcomes included the seven individual scales of the POMS 2, other psychobehavioral measures, physical performance, and laboratory measurements. The trial was registered at the Japan Registry of Clinical Trials (jRCTs071190028). Results: Forty participants (20 in the plasmalogen group and 20 in the placebo group) completed the 4-week treatment. The Total Mood Disturbance (TMD) score of the plasmalogen group showed a greater decrease at 4 weeks than that of the placebo group while the between-group difference was marginally significant (p = 0.07). The anger-hostility and fatigue-inertia scores of the POMS 2 decreased significantly in the plasmalogen group, but not in the placebo group, at 4 weeks. Between-group differences in those scores were highly significant (p = 0.003 for anger-hostility and p = 0.005 for fatigue-inertia). The plasmalogen group showed a slight decrease in the Athens Insomnia Scale at 2 weeks, and the between-group difference was near-significant (p = 0.07). The elapsed time in minute patterns on the Uchida-Kraepelin test, which is a marker of mental concentration, revealed significantly greater performance in the plasmalogen group than in the placebo group. There were no between-group differences in physical and laboratory measurements. Conclusion: It is suggested that orally administered plasmalogens alleviate negative mood states and sleep problems, and also enhance mental concentration.

Clinical and Pathological Benefits of Scallop-Derived Plasmalogen in a Novel Mouse Model of Alzheimer's Disease with Chronic Cerebral Hypoperfusion.

BACKGROUND: The oral ingestion of scallop-derived plasmalogen (sPlas) significantly improved cognitive function in Alzheimer's disease (AD) patients. OBJECTIVE: However, the effects and mechanisms of sPlas on AD with chronic cerebral hypoperfusion (CCH), a class of mixed dementia contributing to 20-30% among the dementia society, were still elusive. METHODS: In the present study, we applied a novel mouse model of AD with CCH to investigate the potential effects of sPlas on AD with CCH. RESULTS: The present study demonstrated that sPlas significantly recovered cerebral blood flow, improved motor and cognitive deficits, reduced amyloid-ß pathology, regulated neuroinflammation, ameliorated neural oxidative stress, and inhibited neuronal loss in AD with CCH mice at 12 M. CONCLUSION: These findings suggest that sPlas possesses clinical and pathological benefits for AD with CCH in the novel model mice. Furthermore, sPlas could have promising prevention and therapeutic effects on patients of AD with CCH.