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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

Osmotin inhibits LPS-induced protein expression of Aβ, APP, BACE-1, and p-Tau.(A) Shown are representative Western blots probed with Aβ, APP, BACE-1, and p-Tau antibodies in the hippocampus of adult mice. The density values are expressed in arbitrary units as the mean ± SEM for the indicated proteins (n = 5 animals per group). (B) Shown are representative photomicrographs of immunofluorescence analyses of Aβ-positive cells in the experimental groups. Images are representative of staining obtained in sections prepared from at least 5 animals per group. All of the panels representing the CA1, CA3, and DG regions of the hippocampus show Aβ-stained brain tissue at a magnification of 10x objective field, scale bar = 50 μm. Symbols for treatment groups and levels of significance are mentioned in the data analysis section of the Materials and Methods.
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f5: Osmotin inhibits LPS-induced protein expression of Aβ, APP, BACE-1, and p-Tau.(A) Shown are representative Western blots probed with Aβ, APP, BACE-1, and p-Tau antibodies in the hippocampus of adult mice. The density values are expressed in arbitrary units as the mean ± SEM for the indicated proteins (n = 5 animals per group). (B) Shown are representative photomicrographs of immunofluorescence analyses of Aβ-positive cells in the experimental groups. Images are representative of staining obtained in sections prepared from at least 5 animals per group. All of the panels representing the CA1, CA3, and DG regions of the hippocampus show Aβ-stained brain tissue at a magnification of 10x objective field, scale bar = 50 μm. Symbols for treatment groups and levels of significance are mentioned in the data analysis section of the Materials and Methods.

Mentions: We examined the effect of LPS and osmotin on the protein expression levels of AD markers, such as Aβ, APP, p-Tau, and BACE-1, in the hippocampus of adult mice. Several studies confirmed that LPS treatment for 1 week in adult rats and mice induced AD-like effects, disrupted synaptic function and impaired memory performance416. Western blots demonstrated that systemic LPS administration significantly increased Aβ and APP levels compared to the control group, and osmotin treatment significantly reversed LPS-induced increases in Aβ and APP levels (Fig. 5A). Our morphological results also demonstrated the anti-AD effect of osmotin. Decreased Aβ levels were observed in the LPS plus osmotin-treated group compared to the LPS-treated group (Fig. 5B). Tau hyperphosphorylation and BACE-1 activation are also critical factors in AD progression. Therefore, we investigated the expression levels of Tau and BACE-1 in LPS- and osmotin-treated mice. Western blot analysis revealed that systemic LPS administration increased the protein expression of p-Tau and BACE-1 enzyme compared to the control group, and osmotin treatment attenuated LPS-induced Tau hyperphosphorylation and BACE-1 enzyme levels (Fig. 5A). These results were also demonstrated in cortical tissue, which also exhibited a significant reduction in Aβ and p-Tau protein expression following osmotin treatment (Fig. S3).


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

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

Osmotin inhibits LPS-induced protein expression of Aβ, APP, BACE-1, and p-Tau.(A) Shown are representative Western blots probed with Aβ, APP, BACE-1, and p-Tau antibodies in the hippocampus of adult mice. The density values are expressed in arbitrary units as the mean ± SEM for the indicated proteins (n = 5 animals per group). (B) Shown are representative photomicrographs of immunofluorescence analyses of Aβ-positive cells in the experimental groups. Images are representative of staining obtained in sections prepared from at least 5 animals per group. All of the panels representing the CA1, CA3, and DG regions of the hippocampus show Aβ-stained brain tissue at a magnification of 10x objective field, scale bar = 50 μm. Symbols for 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

f5: Osmotin inhibits LPS-induced protein expression of Aβ, APP, BACE-1, and p-Tau.(A) Shown are representative Western blots probed with Aβ, APP, BACE-1, and p-Tau antibodies in the hippocampus of adult mice. The density values are expressed in arbitrary units as the mean ± SEM for the indicated proteins (n = 5 animals per group). (B) Shown are representative photomicrographs of immunofluorescence analyses of Aβ-positive cells in the experimental groups. Images are representative of staining obtained in sections prepared from at least 5 animals per group. All of the panels representing the CA1, CA3, and DG regions of the hippocampus show Aβ-stained brain tissue at a magnification of 10x objective field, scale bar = 50 μm. Symbols for treatment groups and levels of significance are mentioned in the data analysis section of the Materials and Methods.
Mentions: We examined the effect of LPS and osmotin on the protein expression levels of AD markers, such as Aβ, APP, p-Tau, and BACE-1, in the hippocampus of adult mice. Several studies confirmed that LPS treatment for 1 week in adult rats and mice induced AD-like effects, disrupted synaptic function and impaired memory performance416. Western blots demonstrated that systemic LPS administration significantly increased Aβ and APP levels compared to the control group, and osmotin treatment significantly reversed LPS-induced increases in Aβ and APP levels (Fig. 5A). Our morphological results also demonstrated the anti-AD effect of osmotin. Decreased Aβ levels were observed in the LPS plus osmotin-treated group compared to the LPS-treated group (Fig. 5B). Tau hyperphosphorylation and BACE-1 activation are also critical factors in AD progression. Therefore, we investigated the expression levels of Tau and BACE-1 in LPS- and osmotin-treated mice. Western blot analysis revealed that systemic LPS administration increased the protein expression of p-Tau and BACE-1 enzyme compared to the control group, and osmotin treatment attenuated LPS-induced Tau hyperphosphorylation and BACE-1 enzyme levels (Fig. 5A). These results were also demonstrated in cortical tissue, which also exhibited a significant reduction in Aβ and p-Tau protein expression following osmotin treatment (Fig. S3).

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