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Cited by 130Neuroinflammation and Neurodegeneration MechanismsAlzheimer's disease research and treatmentsFatty Acid Research and Health

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

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Ifuku, Masataka, Katafuchi, Toshihiko, Mawatari, Shiro, Noda, Mami, Miake, Kiyotaka, Sugiyama, Masaaki, Fujino, Takehiko·2012·Journal of Neuroinflammation
DOI 10.1186/1742-2094-9-197PMC PMC3444880
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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 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.

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Figure 1 Body weight (BW) changes after LPS/Pls administration. BW was measured immediately prior to injection on days 1 to 7 and on day 8 before sacrifice. Filled circle: Con group; open circle: Pls group; filled triangle: LPS group; and open rectangle: LPS + Pls group. Each group, n = 8, **, P <0.1, LPS versus Pls group; #, P <0.05 and ##, P <0.01, LPS versus Con group. Con, control; LPS, lipopolysaccharide; Pls, plasmalogens.
Figure 1 Body weight (BW) changes after LPS/Pls administration. BW was measured immediately prior to injection on days 1 to 7 and on day 8 before sacrifice. Filled circle: Con group; open circle: Pls group; filled triangle: LPS group; and open rectangle: LPS + Pls group. Each group, n = 8, **, P <0.1, LPS versus Pls group; #, P <0.05 and ##, P <0.01, LPS versus Con group. Con, control; LPS, lipopolysaccharide; Pls, plasmalogens.CC BY · PubMed Central
Figure 2 Activation of glial cells in the murine PFC following LPS injection (i.p.) performed on seven consecutive days and suppression by Pls applied immediately after each LPS injection. A, Iba-1-positive microglia (green) and GFAP-positive astrocytes (red). The number and intensity of immunoreactivity of microglia increased after LPS treatment (d) with hypertrophy (d’) compared with that observed in the Con group (a and a’) and was suppressed by application of Pls (g and g’). The Pls group (j and j’) showed no differences from the Con group. GFAP-positive astrocytes also demonstrated increases in number and intensity due to LPS and suppression by Pls (middle column). Iba-1 and GFAP immunostaining did not merge with each other (f). Scale bar: low magnification, 100 μm, and high magnification, 20 μm. B, A summary of LPS-induced increases in the numbers of microglia (left) and astrocytes (right) and suppression by Pls (each bar, n = 8). **, P <0.01, respectively. Con, control; GFAP, glial fibrillary acidic protein; LPS, lipopolysaccharide; PFC, prefrontal cortex; Pls, plasmalogens.
Figure 2 Activation of glial cells in the murine PFC following LPS injection (i.p.) performed on seven consecutive days and suppression by Pls applied immediately after each LPS injection. A, Iba-1-positive microglia (green) and GFAP-positive astrocytes (red). The number and intensity of immunoreactivity of microglia increased after LPS treatment (d) with hypertrophy (d’) compared with that observed in the Con group (a and a’) and was suppressed by application of Pls (g and g’). The Pls group (j and j’) showed no differences from the Con group. GFAP-positive astrocytes also demonstrated increases in number and intensity due to LPS and suppression by Pls (middle column). Iba-1 and GFAP immunostaining did not merge with each other (f). Scale bar: low magnification, 100 μm, and high magnification, 20 μm. B, A summary of LPS-induced increases in the numbers of microglia (left) and astrocytes (right) and suppression by Pls (each bar, n = 8). **, P <0.01, respectively. Con, control; GFAP, glial fibrillary acidic protein; LPS, lipopolysaccharide; PFC, prefrontal cortex; Pls, plasmalogens.CC BY · PubMed Central
Figure 3 Activation of glial cells following LPS (i.p.) injection and suppression by Pls in the murine CA1 region of the hippocampus. A, Iba-1-positive microglia (green) and GFAP-positive astrocytes (red). The number and intensity of immunoreactivity of microglia and astrocytes increased following LPS treatment (d and e) compared with that observed in the Con group (a and b) and was suppressed by Pls (g and h). They did not merge with each other (right column). PyCL: pyramidal cell layer of the hippocampus. Scale bar: 100 μm. B, A summary of LPS-induced increases in the numbers of microglia (left) and astrocytes (right) and suppression by Pls (each bar, n = 8). **, P <0.01. Con, control; GFAP, glial fibrillary acidic protein; i.p., intraperitoneal; LPS, lipopolysaccharide; Pls, plasmalogens.
Figure 3 Activation of glial cells following LPS (i.p.) injection and suppression by Pls in the murine CA1 region of the hippocampus. A, Iba-1-positive microglia (green) and GFAP-positive astrocytes (red). The number and intensity of immunoreactivity of microglia and astrocytes increased following LPS treatment (d and e) compared with that observed in the Con group (a and b) and was suppressed by Pls (g and h). They did not merge with each other (right column). PyCL: pyramidal cell layer of the hippocampus. Scale bar: 100 μm. B, A summary of LPS-induced increases in the numbers of microglia (left) and astrocytes (right) and suppression by Pls (each bar, n = 8). **, P <0.01. Con, control; GFAP, glial fibrillary acidic protein; i.p., intraperitoneal; LPS, lipopolysaccharide; Pls, plasmalogens.CC BY · PubMed Central
Figure 4 Activation of glial cells following LPS (i.p.) injection and suppression by Pls in the murine dentate gyrus of the hippocampus. A, Iba-1-positive microglia (green) and GFAP-positive astrocytes (red). The number and intensity of immunoreactivity of microglia and astrocytes increased following LPS treatment (d and e) compared with that observed in the Con group (a and b) and was suppressed by Pls (g and h). They did not merge with each other (right column). GCL: granule cell layer. Scale bar: 100 μm. B, A summary of LPS-induced increases in the numbers of microglia (left) and astrocytes (right) and suppression by Pls (each bar, n = 8). **, P <0.01. Con, control; GFAP, glial fibrillary acidic protein; i.p., intraperitoneal; LPS, lipopolysaccharide; Pls, plasmalogens.
Figure 4 Activation of glial cells following LPS (i.p.) injection and suppression by Pls in the murine dentate gyrus of the hippocampus. A, Iba-1-positive microglia (green) and GFAP-positive astrocytes (red). The number and intensity of immunoreactivity of microglia and astrocytes increased following LPS treatment (d and e) compared with that observed in the Con group (a and b) and was suppressed by Pls (g and h). They did not merge with each other (right column). GCL: granule cell layer. Scale bar: 100 μm. B, A summary of LPS-induced increases in the numbers of microglia (left) and astrocytes (right) and suppression by Pls (each bar, n = 8). **, P <0.01. Con, control; GFAP, glial fibrillary acidic protein; i.p., intraperitoneal; LPS, lipopolysaccharide; Pls, plasmalogens.CC BY · PubMed Central
Figure 5 Increases in the levels of IL-1β and TNF-α mRNAs following LPS (i.p.) injection and suppression by Pls in the murine PFC and hippocampus. A, Significant increases in the levels of IL-1β (left) and TNF-α (right) mRNAs in the PFC were seen in the LPS group compared with that observed in the other groups (Con, LPS + Pls and Pls groups). B, Significant increases in the levels of IL-1β (left) and TNF-α (right) mRNAs in the hippocampus were seen in the LPS group compared to that observed in the other groups. Each bar, n = 5, **, P <0.01. _Con, control; IL-1β, interleukin-1β; i.p., intraperitoneal; LPS, lipopolysaccharide; PFC, prefrontal cortex; Pls, plasmalogens; TNF-α, tumor necrosis factor α.
Figure 5 Increases in the levels of IL-1β and TNF-α mRNAs following LPS (i.p.) injection and suppression by Pls in the murine PFC and hippocampus. A, Significant increases in the levels of IL-1β (left) and TNF-α (right) mRNAs in the PFC were seen in the LPS group compared with that observed in the other groups (Con, LPS + Pls and Pls groups). B, Significant increases in the levels of IL-1β (left) and TNF-α (right) mRNAs in the hippocampus were seen in the LPS group compared to that observed in the other groups. Each bar, n = 5, **, P <0.01. _Con, control; IL-1β, interleukin-1β; i.p., intraperitoneal; LPS, lipopolysaccharide; PFC, prefrontal cortex; Pls, plasmalogens; TNF-α, tumor necrosis factor α.CC BY · PubMed Central
Figure 6 Accumulation of Aβ proteins following LPS (i.p.) injection and suppression by Pls in the murine PFC. Neurons were stained with NeuN (red). A weak fluorescence for Aβ3–16 immunoreactivity (green) in the Con group (b) increased following LPS treatment (e) and was completely abolished by Pl administration (h). The Aβ3–16 fluorescence merged with the NeuN immunoreactivity, indicating the intracellular localization of Aβ (f). Scale bar: 50 μm. Aβ, β-amyloid; Con, control; i.p., intraperitoneal; LPS, lipopolysaccharide; PFC, prefrontal cortex; Pls, plasmalogens.
Figure 6 Accumulation of Aβ proteins following LPS (i.p.) injection and suppression by Pls in the murine PFC. Neurons were stained with NeuN (red). A weak fluorescence for Aβ3–16 immunoreactivity (green) in the Con group (b) increased following LPS treatment (e) and was completely abolished by Pl administration (h). The Aβ3–16 fluorescence merged with the NeuN immunoreactivity, indicating the intracellular localization of Aβ (f). Scale bar: 50 μm. Aβ, β-amyloid; Con, control; i.p., intraperitoneal; LPS, lipopolysaccharide; PFC, prefrontal cortex; Pls, plasmalogens.CC BY · PubMed Central
Figure 7 Accumulation of Aβ proteins following LPS (i.p.) injection and suppression by Pls in the murine CA1 region of the hippocampus. Neurons were stained with NeuN (red). A weak fluorescence for Aβ3–16 immunoreactivity (green) in the Con group (b) increased following LPS treatment (e) and was markedly attenuated by Pl administration (h). The Aβ3–16 fluorescence merged with the NeuN immunoreactivity, indicating the intracellular localization of Aβ (f and i). Scale bar: 50 μm. Aβ, β-amyloid; Con, control; i.p., intraperitoneal; LPS, lipopolysaccharide; Pls, plasmalogens.
Figure 7 Accumulation of Aβ proteins following LPS (i.p.) injection and suppression by Pls in the murine CA1 region of the hippocampus. Neurons were stained with NeuN (red). A weak fluorescence for Aβ3–16 immunoreactivity (green) in the Con group (b) increased following LPS treatment (e) and was markedly attenuated by Pl administration (h). The Aβ3–16 fluorescence merged with the NeuN immunoreactivity, indicating the intracellular localization of Aβ (f and i). Scale bar: 50 μm. Aβ, β-amyloid; Con, control; i.p., intraperitoneal; LPS, lipopolysaccharide; Pls, plasmalogens.CC BY · PubMed Central

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Authors
Ifuku, M., Katafuchi, T., Mawatari, S., Noda, M., Miake, K., Sugiyama, M., & Fujino, T.
Affiliations
  • Kyushu University (JP)
  • Institute of Rheological Functions of Food (JP)
  • Marudai FOOD Co., Ltd. (Japan) (JP)
Corresponding author
Katafuchi, Toshihiko
ORCID
Venue
Journal of Neuroinflammation
Publisher
Springer Science and Business Media LLC
Published
2012-08-13
Volume
9
Issue
1
Pages
197-197
ISSN
1742-2094 (ISSN-L)
DOI
10.1186/1742-2094-9-197
PMC
PMC3444880
OpenAlex
W2037650763
Cited by
130
References
60
Citations by year
2026: 7 · 2025: 8 · 2024: 13 · 2023: 8 · 2022: 12 · 2021: 15 · 2020: 11 · 2019: 13 · 2018: 12 · 2017: 9 · 2016: 6 · 2015: 6 · 2014: 5 · 2013: 5
FWCI
2.57
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Neuroinflammation (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
  • Ministry of Education, Culture, Sports, Science and Technology
  • Japan Society for the Promotion of Science (22590084, 22590225)
Topics
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
  • Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
Keywords
plasmalogens, neuroinflammation, lipopolysaccharide, Alzheimer's disease, amyloid-beta, microglial activation, astrocytes, glycerophospholipids, prefrontal cortex, hippocampus, IL-1β, TNF-α, anti-inflammatory activity
MeSH terms
Animals, Anti-Inflammatory Agents, Brain Edema, Chickens, Inflammation, Lipopolysaccharides, Male, Mice, Inbred C57BL, Plasmalogens, Amyloid beta-Peptides, Glycerophospholipids, Mice

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