Anti-inflammatory/anti-amyloidogenic effects of plasmalogens in lipopolysaccharide-induced neuroinflammation in adult mice

Ifuku Masataka, Katafuchi Toshihiko, Mawatari Shiro, Noda Mami, Miake Kiyotaka, Sugiyama Masaaki, Fujino, Fujino Takehiko

Description

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 (Aβ 3–16 )-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.

Sujets

• Phospholipid
• Microglía
• Alzheimer's disease

Informations

• Publié par: biomed
• Publié le: 01 janvier 2012
• Nombre de lectures: 8
• Langue: English
• Poids de l'ouvrage: 5 Mo

Extrait

Ifuku et al. Journal of Neuroinflammation 2012, 9 :197 http://www.jneuroinflammation.com/content/9/1/197

JOURNAL OF NEUROINFLAMMATION

R E S E A R C H Open Access Anti-inflammatory/anti-amyloidogenic effects of plasmalogens in lipopolysaccharide-induced neuroinflammation in adult mice Masataka Ifuku 1 , Toshihiko Katafuchi 1* , Shiro Mawatari 2 , Mami Noda 3 , Kiyotaka Miake 4 , Masaaki Sugiyama 4 and Takehiko Fujino 2

Abstract 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 μ g/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-1 β and TNF-α mRNAs. In addition, β -amyloid (A β 3 – 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 A β 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. Keywords: Neuroinflammation, Phospholipids, Microglia, Alzheimer ’ s disease

Background key rate-limiting enzyme that initiates A β formation, It has been demonstrated in mice and rats that the sys- and the concentration of brain A β 1 – 42 in adult but not temic administration of lipopolysaccharide (LPS) and young mice [1]. Furthermore, the intracellular accumula- polyriboinosinic:polyribocytidylic acid (poly I:C), ligands tion of A β 1 – 42 in hippocampal pyramidal neurons fol- for toll-like receptor (TLR) 4 and TLR 3, respectively, in- lowing daily injections of LPS for seven days has been duce neuroinflammation in the central nervous system immunohistochemically demonstrated [1]. Although the (CNS), thus leading to neurodegeneration, the suppres- precise mechanisms underlying LPS-induced amyloido- sion of neurogenesis and the impairment of cognitive genesis have not yet been determined, it is likely that behavior [1-3]. One of the possible mechanisms of neu- proinflammatory cytokines such as IL-1 β , TNF-α , IFN-γ , roinflammation may be the production of β -amyloid and reactive oxygen/nitrogen species (ROS/RNS) proteins (A β ). For example, a single intraperitoneal (i.p.) released from activated glial cells play significant roles in injection of LPS increases the activity of β -secretase, a A β formation, which are suppressed by NSAIDs through the activation of peroxisome proliferator-activated recep- 1 * D C e o p r a r r e t s m po e n nt de o n f c In e: te k g a r t a a t f i @ ve ph P y h s y io si l. ol m o e g d y . , ky G u r s a h d u u - a u t . e ac S .j c p holofMedicalSciences, tor-γ (PPAR-γ )[4- s 6 ) ]. areuniqueglycerophospholipidsthat KyushuUniversity,Fukuoka io 8 n 1 i 2 s -8 a 5 v 8 ai 2 l , a J b a le pa a n ttheend o ofthearticle Plas in ma a log v ens l (P e l therbondatthe sn -1 position of the Full list of author informat conta iny © 2012 Ifuku et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.