Anti-inflammatory/anti-amyloidogenic effects of plasmalogens in lipopolysaccharide-induced neuroinflammation in adult mice.
BACKGROUND
Neuroinflammation involves the activation of glial cells in neurodegenerative diseases such as Alzheimer's disease (AD). Plasmalogens (Pls) are glycerophospholipids constituting cellular membranes and play significant roles in membrane fluidity and cellular processes such as vesicular fusion and signal transduction.


METHODS
In this study the preventive effects of Pls on systemic lipopolysaccharide (LPS)-induced neuroinflammation were investigated using immunohistochemistry, real-time PCR methods and analysis of brain glycerophospholipid levels in adult mice.


RESULTS
Intraperitoneal (i.p.) injections of LPS (250 μg/kg) for seven days resulted in increases in the number of Iba-1-positive microglia and glial fibrillary acidic protein (GFAP)-positive astrocytes in the prefrontal cortex (PFC) and hippocampus accompanied by the enhanced expression of IL-1β and TNF-α mRNAs. In addition, β-amyloid (Aβ3-16)-positive neurons appeared in the PFC and hippocampus of LPS-injected animals. The co-administration of Pls (i.p., 20 mg/kg) after daily LPS injections significantly attenuated both the activation of glial cells and the accumulation of Aβ proteins. Finally, the amount of Pls in the PFC and hippocampus decreased following the LPS injections and this reduction was suppressed by co-treatment with Pls.


CONCLUSIONS
These findings suggest that Pls have anti-neuroinflammatory and anti-amyloidogenic effects, thereby indicating the preventive or therapeutic application of Pls against AD.
Department of Integrative Physiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
Masataka
M
Ifuku
Toshihiko
T
Katafuchi
Shiro
S
Mawatari
Mami
M
Noda
Kiyotaka
K
Miake
Masaaki
M
Sugiyama
Takehiko
T
Fujino
D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D001929:Brain Edema / Q000188:drug therapy*; D002645:Chickens; D020404:Glycerophospholipids / Q000627:therapeutic use; D007249:Inflammation / Q000188:drug therapy / Q000473:pathology; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010955:Plasmalogens / Q000627:therapeutic use*
D016229:Amyloid beta-Peptides; D000893:Anti-Inflammatory Agents; D020404:Glycerophospholipids; D008070:Lipopolysaccharides; D010955:Plasmalogens