• 2018-07
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  • 2020-01
  • Regarding the change of blood Pls levels after


    Regarding the change of blood Pls levels after treatment, there were significant differences between the treatment and placebo groups in mild AD patients. Plasma PlsPE in the placebo group decreased significantly after treatment, whereas that of the treatment group remained unchanged. Some studies suggest that statins, a class of cholesterol-lowering drugs, raise blood level of PlsPE (Meikle et al., 2015). In the present study, 23 (23.5%) of 98 patients with mild AD used statins during the study period. However, there were still significant differences in the changes of plasma PlsPE between the treatment and placebo groups except for statin-users. Therefore, it is unlikely that statins protected the decrease of Plasma PlsPE in the treatment group. These results might indicate that Pls production in peroxisome was concurrently reduced with the progression of Alzheimer\'s disease during the 24-week treatment period, and suggest that orally administered Pls may contribute to maintain the production of Pls in peroxisome.
    Funding Sources The study was funded by The Japanese Plasmalogen Society (Pls2014-01) (Fukuoka, Japan) as an investigator-initiated trial.
    Conflicts of Interest
    Author Contributions
    Introduction Febrile seizures (FS) are the most common type of seizure in childhood (Shinnar, 1998; Sillanpaa et al., 1998). Retrospective clinical studies have demonstrated a significant relationship between a history of prolonged FS during early childhood and mesial temporal sclerosis, which is responsible for intractable temporal lobe epilepsy (Cendes et al., 1993). However, it is difficult in clinical studies to separate the effect of the FS itself (e.g., seizure type, number, and duration) from the effect of preexisting nucleoside transporters pathology (e.g. genetic or acquired factors) and the influence of treatment. Well-established models have been developed, in which FS are evoked by exposing rat pups to a hyperthermic environment that raises the body temperature to a level comparable with human fever (Baram et al., 1997; Holtzman et al., 1981; Chen et al., 1999; Dube et al., 2000). Using these models, studies have shown that 100% of FS rats show enhanced susceptibility to kainic acid (KA)-induced seizures (Dube et al., 2000, 2006, 2010). Recently, our study also demonstrated that infantile FS mice showed decreased generalized seizures threshold induced by maximal electro-shock (MES) (Siedlecki & Zielenkiewicz, 2006). However, whether the enhancement of susceptibility is widely existed and maintained for long time and how this phenomenon occurs are still unknown. It has been demonstrated that exposing young animals to an enriched environment enhances the magnitude of LTP induction in the CA1 hippocampus of themselves as well as their future offspring, even if the offspring are not exposed to enriched environment. Furthermore, it is demonstrated that behavioral and emotional disorders acquired from early-life adverse environmental experiences can be transmitted to their unaffected offspring (Sterba et al., 2007; Kim et al., 2009; Arai et al., 2009). These findings suggest that the acquired enhancement of neuroplasticity can be transmitted to offspring. As neuroplasticity plays an important role in the development of a chronic seizure state (Bough et al., 2004; Schwartzkroin, 2001). Thus a key question is whether the enhanced seizure susceptibility induced by early life FS transmitted to their unaffected offspring and the underlie characteristic of this transgenerational transmission. Previously studies have shown that early-life environmental exposure led to epigenetic changes which even transgenerational transmission to their unaffected offspring (Jirtle & Skinner, 2007; Skinner et al., 2010; Bohacek et al., 2013). FS was also a disease induced by early-life hyperthermia environmental exposure. Here we investigated whether DNA methylation, a main composition of epigenetic modification, participated in the enhanced seizure susceptibility induced by serious FSs in affected adult rats and their offspring.