Effects of plasmalogens on systemic lipopolysaccharide‐induced glial activation and β‐amyloid accumulation in adult mice

Katafuchi, Toshihiko; Ifuku, Masataka; Shiro, Motoo; Нода, Мами; Miake, K; Sugiyama, Masaaki; Fujino, Takehiko

doi:10.1111/j.1749-6632.2012.06641.x

Cited by 60 publications

(44 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Moreover, innate immune-mediated neuroinflammation also occurs in company with Aβ accumulation in AD, which often leads to abundant inflammatory cells, including glial activation that expresses high levels of glucose transporters and thus increases brain glycolytic activity [23,24,25]. Our study revealed the entorhinal cortex and hippocampus as regions affected first with glucose disorders, perhaps because these regions are highly dependent on the insulin signaling pathway and are initially subject to Aβ accumulation [26,27]. While accumulated Aβ causes glucose metabolic disorder by disturbing the insulin signaling pathway, altered glucose metabolism can conversely promote Aβ accumulation.…”

Section: Discussionmentioning

confidence: 98%

Age- and Brain Region-Specific Changes of Glucose Metabolic Disorder, Learning, and Memory Dysfunction in Early Alzheimer’s Disease Assessed in APP/PS1 Transgenic Mice Using 18F-FDG-PET

Men

Zhu

et al. 2016

IJMS

View full text Add to dashboard Cite

Alzheimer’s disease (AD) is a leading cause of dementia worldwide, associated with cognitive deficits and brain glucose metabolic alteration. However, the associations of glucose metabolic changes with cognitive dysfunction are less detailed. Here, we examined the brains of APP/presenilin 1 (PS1) transgenic (Tg) mice aged 2, 3.5, 5 and 8 months using 18F-labed fluorodeoxyglucose (18F-FDG) microPET to assess age- and brain region-specific changes of glucose metabolism. FDG uptake was calculated as a relative standardized uptake value (SUVr). Morris water maze (MWM) was used to evaluate learning and memory dysfunction. We showed a glucose utilization increase in multiple brain regions of Tg mice at 2 and 3.5 months but not at 5 and 8 months. Comparisons of SUVrs within brains showed higher glucose utilization than controls in the entorhinal cortex, hippocampus, and frontal cortex of Tg mice at 2 and 3.5 months but in the thalamus and striatum at 3.5, 5 and 8 months. By comparing SUVrs in the entorhinal cortex and hippocampus, Tg mice were distinguished from controls at 2 and 3.5 months. In MWM, Tg mice aged 2 months shared a similar performance to the controls (prodromal-AD). By contrast, Tg mice failed training tests at 3.5 months but failed all MWM tests at 5 and 8 months, suggestive of partial or complete cognitive deficits (symptomatic-AD). Correlation analyses showed that hippocampal SUVrs were significantly correlated with MWM parameters in the symptomatic-AD stage. These data suggest that glucose metabolic disorder occurs before onset of AD signs in APP/PS1 mice with the entorhinal cortex and hippocampus affected first, and that regional FDG uptake increase can be an early biomarker for AD. Furthermore, hippocampal FDG uptake is a possible indicator for progression of Alzheimer’s cognition after cognitive decline, at least in animals.

show abstract

Section: Discussionmentioning

confidence: 98%

Age- and Brain Region-Specific Changes of Glucose Metabolic Disorder, Learning, and Memory Dysfunction in Early Alzheimer’s Disease Assessed in APP/PS1 Transgenic Mice Using 18F-FDG-PET

Men

Zhu

et al. 2016

IJMS

View full text Add to dashboard Cite

show abstract

“…However, it is not clear whether the decrease of Pls in brain tissue and in plasma is the cause of the disease or merely a result of the disease. Recent studies of animal models of AD by our group indicated that intraperitoneal administration of purified Pls improved cognitive function (Katafuchi et al, 2012, Hossain et al, 2013, Hossain et al, 2016). …”

Section: Introductionmentioning

confidence: 99%

Efficacy and Blood Plasmalogen Changes by Oral Administration of Plasmalogen in Patients with Mild Alzheimer's Disease and Mild Cognitive Impairment: A Multicenter, Randomized, Double-blind, Placebo-controlled Trial

Yamada²,

et al. 2017

Self Cite

View full text Add to dashboard Cite

BackgroundPlasmalogens (Pls) reportedly decreased in postmortem brain and in the blood of patients with Alzheimer's disease (AD). Recently we showed that intraperitoneal administration of Pls improved cognitive function in experimental animals. In the present trial, we tested the efficacy of oral administration of scallop-derived purified Pls with respect to cognitive function and blood Pls changes in patients with mild AD and mild cognitive impairment (MCI).MethodsThe study was a multicenter, randomized, double-blind, placebo-controlled trial of 24 weeks. Participants were 328 patients aged 60 to 85 years who had 20 to 27 points in Mini Mental State Examination-Japanese (MMSE-J) score and five or less points in Geriatric Depression Scale-Short Version-Japanese (GDS-S-J). They were randomized to receive either 1 mg/day of Pls purified from scallop or placebo. The patients and study physicians were masked to the assignment. The primary outcome was MMSE-J. The secondary outcomes included Wechsler Memory Scale-Revised (WMS-R), GDS-S-J and concentration of phosphatidyl ethanolamine plasmalogens (PlsPE) in erythrocyte membrane and plasma. This trial is registered with the University Hospital Medical Information Network, number UMIN000014945.FindingsOf 328 patients enrolled, 276 patients completed the trial (140 in the treatment group and 136 in the placebo group). In an intention-to-treat analysis including both mild AD (20 ≤ MMSE-J ≤ 23) and MCI (24 ≤ MMSE-J ≤ 27), no significant difference was shown between the treatment and placebo groups in the primary and secondary outcomes, with no severe adverse events in either group. In mild AD patients, WMS-R improved significantly in the treatment group, and the between group difference was nearly significant (P = 0.067). In a subgroup analysis of mild AD patients, WMS-R significantly improved among females and those aged below 77 years in the treatment group, and the between-group differences were statistically significant in females (P = 0.017) and in those aged below 77 years (P = 0.029). Patients with mild AD showed a significantly greater decrease in plasma PlsPE in the placebo group than in the treatment group.InterpretationOral administration of scallop-derived purified Pls may improve cognitive functions of mild AD.Funding.

show abstract

“…Plasmalogens (Pls) constitute a special class of glycerophospholipids characterized by the presence of a vinyl ether linkage at the sn-1 position of the glycerol backbone [1-4]. Pls are found in various human tissues including their major presence in the nervous, cardiovascular and immune systems [1,4].…”

Section: Introductionmentioning

confidence: 99%

Plasmalogens Rescue Neuronal Cell Death through an Activation of AKT and ERK Survival Signaling

et al. 2013

Self Cite

View full text Add to dashboard Cite

Neuronal cells are susceptible to many stresses, which will cause the apoptosis and neurodegenerative diseases. The precise molecular mechanism behind the neuronal protection against these apoptotic stimuli is necessary for drug discovery. In the present study, we have found that plasmalogens (Pls), which are glycerophospholipids containing vinyl ether linkage at sn-1 position, can protect the neuronal cell death upon serum deprivation. Interestingly, caspse-9, but not caspase-8 and caspase-12, was cleaved upon the serum starvation in Neuro-2A cells. Pls treatments effectively reduced the activation of caspase-9. Furthermore, cellular signaling experiments showed that Pls enhanced phosphorylation of the phosphoinositide 3-kinase (PI3K)-dependent serine/threonine-specific protein kinase AKT and extracellular-signal-regulated kinases ERK1/2. PI3K/AKT inhibitor LY294002 and MAPK/ERK kinase (MEK) inhibitor U0126 treatments study clearly indicated that Pls-mediated cell survival was dependent on the activation of these kinases. In addition, Pls also inhibited primary mouse hippocampal neuronal cell death induced by nutrient deprivation, which was associated with the inhibition of caspase-9 and caspase-3 cleavages. It was reported that Pls content decreased in the brain of the Alzheimer’s patients, which indicated that the reduction of Pls content could endanger neurons. The present findings, taken together, suggest that Pls have an anti-apoptotic action in the brain. Further studies on precise mechanisms of Pls-mediated protection against cell death may lead us to establish a novel therapeutic approach to cure neurodegenerative disorders.

show abstract

Effects of plasmalogens on systemic lipopolysaccharide‐induced glial activation and β‐amyloid accumulation in adult mice

Cited by 60 publications

References 52 publications

Age- and Brain Region-Specific Changes of Glucose Metabolic Disorder, Learning, and Memory Dysfunction in Early Alzheimer’s Disease Assessed in APP/PS1 Transgenic Mice Using 18F-FDG-PET

Age- and Brain Region-Specific Changes of Glucose Metabolic Disorder, Learning, and Memory Dysfunction in Early Alzheimer’s Disease Assessed in APP/PS1 Transgenic Mice Using 18F-FDG-PET

Efficacy and Blood Plasmalogen Changes by Oral Administration of Plasmalogen in Patients with Mild Alzheimer's Disease and Mild Cognitive Impairment: A Multicenter, Randomized, Double-blind, Placebo-controlled Trial

Plasmalogens Rescue Neuronal Cell Death through an Activation of AKT and ERK Survival Signaling

Contact Info

Product

Resources

About