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Osmotin attenuates LPS-induced neuroinflammation and memory impairments via the TLR4/NFκB signaling pathway.

Badshah H, Ali T, Kim MO - Sci Rep (2016)

Bottom Line: Osmotin improved synaptic functionality via enhancing the activity of pre- and post-synaptic markers, like PSD-95, SNAP-25, and syntaxin-1.Osmotin also prevented LPS-induced apoptotic neurodegeneration via inhibition of PARP-1 and caspase-3.Overall, our studies demonstrated that osmotin prevented neuroinflammation-associated memory impairment and neurodegeneration and suggest AdipoR1 as a therapeutic target for the treatment of neuroinflammation and neurological disorders, such as AD.

View Article: PubMed Central - PubMed

Affiliation: Division of Applied Life Science (BK 21), College of Natural Sciences (RINS), Gyeongsang National University, Jinju, 660-701, Republic of Korea.

ABSTRACT
Toll-like receptor 4 (TLR4) signaling in the brain mediates autoimmune responses and induces neuroinflammation that results in neurodegenerative diseases, such as Alzheimer's disease (AD). The plant hormone osmotin inhibited lipopolysaccharide (LPS)-induced TLR4 downstream signaling, including activation of TLR4, CD14, IKKα/β, and NFκB, and the release of inflammatory mediators, such as COX-2, TNF-α, iNOS, and IL-1β. Immunoprecipitation demonstrated colocalization of TLR4 and AdipoR1 receptors in BV2 microglial cells, which suggests that osmotin binds to AdipoR1 and inhibits downstream TLR4 signaling. Furthermore, osmotin treatment reversed LPS-induced behavioral and memory disturbances and attenuated LPS-induced increases in the expression of AD markers, such as Aβ, APP, BACE-1, and p-Tau. Osmotin improved synaptic functionality via enhancing the activity of pre- and post-synaptic markers, like PSD-95, SNAP-25, and syntaxin-1. Osmotin also prevented LPS-induced apoptotic neurodegeneration via inhibition of PARP-1 and caspase-3. Overall, our studies demonstrated that osmotin prevented neuroinflammation-associated memory impairment and neurodegeneration and suggest AdipoR1 as a therapeutic target for the treatment of neuroinflammation and neurological disorders, such as AD.

No MeSH data available.


Related in: MedlinePlus

Effect of osmotin on LPS-induced activation of astrocytes and microglia in the hippocampus of adult mice.Shown are representative photomicrographs of immunofluorescence analyses of (A) astrocytes (GFAP-positive cells) and (B) microglia (Iba-1-positive cells) in the experimental groups. Images are representative of staining obtained in sections prepared from at least 5 animals per group. Panels representing the hippocampal fissure and DG region of the hippocampus show GFAP and Iba-1 stained brain tissue, respectively, at a magnification of 10x objective field, scale bar = 100 μm. Symbols for the treatment groups and levels of significance are mentioned in the data analysis section of the Materials and Methods.
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f4: Effect of osmotin on LPS-induced activation of astrocytes and microglia in the hippocampus of adult mice.Shown are representative photomicrographs of immunofluorescence analyses of (A) astrocytes (GFAP-positive cells) and (B) microglia (Iba-1-positive cells) in the experimental groups. Images are representative of staining obtained in sections prepared from at least 5 animals per group. Panels representing the hippocampal fissure and DG region of the hippocampus show GFAP and Iba-1 stained brain tissue, respectively, at a magnification of 10x objective field, scale bar = 100 μm. Symbols for the treatment groups and levels of significance are mentioned in the data analysis section of the Materials and Methods.

Mentions: The activation of microglia and astrocytes are the major elements for the progression of neuroinflammation, and activated glial cells are pools for the released inflammatory cytokines2829. LPS treatment activates microglia and astrocytes in vitro or in vivo230. Therefore, we investigated the inhibitory effect of osmotin on LPS-induced astrocytes and microglial activation. Confocal microscopy revealed that systemic LPS administration significantly increased the number of activated astrocytes (GFAP-reactive cells) and microglia (Iba-1-reactive cells) in the cortex and hippocampus of adult mice. Osmotin treatment attenuated the expression of GFAP- and Iba-1-reactive cells compared to the LPS-treated group (Fig. 4).


Osmotin attenuates LPS-induced neuroinflammation and memory impairments via the TLR4/NFκB signaling pathway.

Badshah H, Ali T, Kim MO - Sci Rep (2016)

Effect of osmotin on LPS-induced activation of astrocytes and microglia in the hippocampus of adult mice.Shown are representative photomicrographs of immunofluorescence analyses of (A) astrocytes (GFAP-positive cells) and (B) microglia (Iba-1-positive cells) in the experimental groups. Images are representative of staining obtained in sections prepared from at least 5 animals per group. Panels representing the hippocampal fissure and DG region of the hippocampus show GFAP and Iba-1 stained brain tissue, respectively, at a magnification of 10x objective field, scale bar = 100 μm. Symbols for the treatment groups and levels of significance are mentioned in the data analysis section of the Materials and Methods.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4837357&req=5

f4: Effect of osmotin on LPS-induced activation of astrocytes and microglia in the hippocampus of adult mice.Shown are representative photomicrographs of immunofluorescence analyses of (A) astrocytes (GFAP-positive cells) and (B) microglia (Iba-1-positive cells) in the experimental groups. Images are representative of staining obtained in sections prepared from at least 5 animals per group. Panels representing the hippocampal fissure and DG region of the hippocampus show GFAP and Iba-1 stained brain tissue, respectively, at a magnification of 10x objective field, scale bar = 100 μm. Symbols for the treatment groups and levels of significance are mentioned in the data analysis section of the Materials and Methods.
Mentions: The activation of microglia and astrocytes are the major elements for the progression of neuroinflammation, and activated glial cells are pools for the released inflammatory cytokines2829. LPS treatment activates microglia and astrocytes in vitro or in vivo230. Therefore, we investigated the inhibitory effect of osmotin on LPS-induced astrocytes and microglial activation. Confocal microscopy revealed that systemic LPS administration significantly increased the number of activated astrocytes (GFAP-reactive cells) and microglia (Iba-1-reactive cells) in the cortex and hippocampus of adult mice. Osmotin treatment attenuated the expression of GFAP- and Iba-1-reactive cells compared to the LPS-treated group (Fig. 4).

Bottom Line: Osmotin improved synaptic functionality via enhancing the activity of pre- and post-synaptic markers, like PSD-95, SNAP-25, and syntaxin-1.Osmotin also prevented LPS-induced apoptotic neurodegeneration via inhibition of PARP-1 and caspase-3.Overall, our studies demonstrated that osmotin prevented neuroinflammation-associated memory impairment and neurodegeneration and suggest AdipoR1 as a therapeutic target for the treatment of neuroinflammation and neurological disorders, such as AD.

View Article: PubMed Central - PubMed

Affiliation: Division of Applied Life Science (BK 21), College of Natural Sciences (RINS), Gyeongsang National University, Jinju, 660-701, Republic of Korea.

ABSTRACT
Toll-like receptor 4 (TLR4) signaling in the brain mediates autoimmune responses and induces neuroinflammation that results in neurodegenerative diseases, such as Alzheimer's disease (AD). The plant hormone osmotin inhibited lipopolysaccharide (LPS)-induced TLR4 downstream signaling, including activation of TLR4, CD14, IKKα/β, and NFκB, and the release of inflammatory mediators, such as COX-2, TNF-α, iNOS, and IL-1β. Immunoprecipitation demonstrated colocalization of TLR4 and AdipoR1 receptors in BV2 microglial cells, which suggests that osmotin binds to AdipoR1 and inhibits downstream TLR4 signaling. Furthermore, osmotin treatment reversed LPS-induced behavioral and memory disturbances and attenuated LPS-induced increases in the expression of AD markers, such as Aβ, APP, BACE-1, and p-Tau. Osmotin improved synaptic functionality via enhancing the activity of pre- and post-synaptic markers, like PSD-95, SNAP-25, and syntaxin-1. Osmotin also prevented LPS-induced apoptotic neurodegeneration via inhibition of PARP-1 and caspase-3. Overall, our studies demonstrated that osmotin prevented neuroinflammation-associated memory impairment and neurodegeneration and suggest AdipoR1 as a therapeutic target for the treatment of neuroinflammation and neurological disorders, such as AD.

No MeSH data available.


Related in: MedlinePlus