RRC ID 18943
著者 Yaguchi T, Nagata T, Nishizaki T.
タイトル 1,2-dilinoleoyl-sn-glycero-3-phosphoethanolamine ameliorates age-related spatial memory deterioration by preventing neuronal cell death.
ジャーナル Behav Brain Funct
Abstract BACKGROUND:Accumulating evidence has pointed that a variety of lipids could exert their beneficial actions against dementia including Alzheimer disease and age-related cognitive decline via diverse signaling pathways. Endoplasmic reticulum (ER) stress-induced neuronal apoptosis, on the other hand, is a critical factor for pathogenesis of neurodegenerative diseases such as Alzheimer disease and Parkinson disease, senile dementia, and ischemic neuronal damage. The present study examined the effects of 1,2-dilinoleoyl-sn-glycero-3-phosphoethanolamine (DLPhtEtn), a phospholipid, on ER stress-induced neuronal death and age-related cognitive disorders.
METHODS:PC-12 cell viability was assayed before and after treatment with amyloid-β(1-40) peptide or thapsigargin in the presence and absence of DLPhtEtn. A series of behavioral tests were performed for senescence-accelerated mouse-prone 8 (SAMP8) mice after 7-month oral administration with polyethylene glycol (PEG) or DLPhtEtn and then, the number of hippocampal neurons was counted.
RESULTS:Amyloid-β(1-40) peptide or thapsigargin is capable of causing ER stress-induced apoptosis. DLPhtEtn (30 μM) significantly inhibited PC-12 cell death induced by amyloid-β(1-40) peptide or thapsigargin. In the water maze test, oral administration with DLPhtEtn (1 mg/kg) for 7 months (three times a week) significantly shortened the prolonged retention latency for SAMP8 mice. In contrast, DLPhtEtn had no effect on the acquisition and retention latencies in both the open field test and the passive avoidance test for SAMP8 mice. Oral administration with DLPhtEtn (1 mg/kg) for 7 months prevented a decrease in the number of hippocampal neurons for SAMP8 mice.
CONCLUSION:The results of the present study show that DLPhtEtn ameliorates age-related spatial memory decline without affecting motor activities or fear memory, possibly by protecting hippocampal neuronal death. DLPhtEtn, thus, might exert its beneficial action against senile dementia and neurodegenerative diseases such as Alzheimer disease.
巻・号 6
ページ 52
公開日 2010-9-13
DOI 10.1186/1744-9081-6-52
PII 1744-9081-6-52
PMID 20831835
PMC PMC2949705
MeSH Age Factors Amyloid beta-Peptides / pharmacology Animals Cell Death / drug effects* Cell Survival / drug effects* Disease Models, Animal Drug Administration Schedule Hippocampus / drug effects* Hippocampus / pathology Male Memory Disorders / pathology* Memory Disorders / prevention & control* Mice Mice, Inbred Strains Neurons / pathology* PC12 Cells Peptide Fragments / pharmacology Phosphatidylethanolamines / administration & dosage Phosphatidylethanolamines / pharmacology* Rats Thapsigargin / pharmacology
IF 2.125
引用数 14
WOS 分野 BEHAVIORAL SCIENCES NEUROSCIENCES
リソース情報
ヒト・動物細胞 PC-12(RCB0009)