1,2-dilinoleoyl-sn-glycero-3-phosphoethanolamine ameliorates age-related spatial memory deterioration by preventing neuronal cell death.
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.


CONCLUSIONS
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.
Yaguchi
Takahiro
T
Division of Bioinformation, Department of Physiology, Hyogo College of Medicine, Nishinomiya, Japan.
Nagata
Tetsu
T
Nishizaki
Tomoyuki
T
D000367:Age Factors; D016229:Amyloid beta-Peptides / Q000494:pharmacology; D000818:Animals; D016923:Cell Death / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects*; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D006624:Hippocampus / Q000187:drug effects* / Q000473:pathology; D008297:Male; D008569:Memory Disorders / Q000473:pathology* / Q000517:prevention & control*; D051379:Mice; D008815:Mice, Inbred Strains; D009474:Neurons / Q000473:pathology*; D016716:PC12 Cells; D010446:Peptide Fragments / Q000494:pharmacology; D010714:Phosphatidylethanolamines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D019284:Thapsigargin / Q000494:pharmacology
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D010714:Phosphatidylethanolamines; C078592:amyloid beta-protein (1-40); C038191:1,2-dilinoleoyl-3-phosphatidylethanolamine; D019284:Thapsigargin