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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 synaptic dysfunction and memory impairment.(A) Shown are representative Western blots probed with PSD-95, SNAP-25, SYP, and syntaxin-1 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 analysis of PSD-95- and SNAP-25-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 hippocampus show PSD-95- and SNAP-25-stained brain tissue at a magnification of 10x objective field, scale bar = 50 μm. Symbols for treatment groups and level of significance are mentioned in the data analysis section of the Materials and Methods. (C) Behavioral studies show osmotin improves memory impairment in LPS-treated mice (n = 5 per group). (a) Average escape latency time for experimental mice to reach the hidden platform from day 3 to day 8. (b) The number of crossings at the hidden platform during the probe test of the Morris water maze experiment. (c) Time spent in the platform quadrant, where the hidden platform was placed during the trial session. Symbols for treatment groups and levels of significance are mentioned in the data analysis section of the Materials and Methods.
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f6: Effect of osmotin on LPS-induced synaptic dysfunction and memory impairment.(A) Shown are representative Western blots probed with PSD-95, SNAP-25, SYP, and syntaxin-1 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 analysis of PSD-95- and SNAP-25-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 hippocampus show PSD-95- and SNAP-25-stained brain tissue at a magnification of 10x objective field, scale bar = 50 μm. Symbols for treatment groups and level of significance are mentioned in the data analysis section of the Materials and Methods. (C) Behavioral studies show osmotin improves memory impairment in LPS-treated mice (n = 5 per group). (a) Average escape latency time for experimental mice to reach the hidden platform from day 3 to day 8. (b) The number of crossings at the hidden platform during the probe test of the Morris water maze experiment. (c) Time spent in the platform quadrant, where the hidden platform was placed during the trial session. Symbols for treatment groups and levels of significance are mentioned in the data analysis section of the Materials and Methods.

Mentions: Recent studies demonstrated that disruption of synaptic function is a primary feature of AD and causes cognitive dysfunction and memory impairment with or without the induction of neurodegeneration31. Therefore, we investigated the effect of LPS and osmotin on postsynaptic (PSD-95) and presynaptic proteins, such as synaptophysin (SYP), synaptosomal associated protein (SNAP-25), and syntaxin-1. Western blot analyses revealed that systemic LPS administration decreased protein levels of PSD-95, SYP, SNAP-25, and syntaxin-1 in the hippocampus of adult mice compared to the control group. Osmotin treatment reversed the LPS-induced effect on synaptic markers and increased the expression of PSD-95, SYP, SNAP-25, and syntaxin-1 compared to the LPS-treated group (Fig. 6A). Immunofluorescence analyses also demonstrated the protective effect of osmotin on LPS-induced synaptic dysfunction. Confocal microscopy revealed a decrease in the fluorescence signals of SNAP-25 and PSD-95 in the hippocampus of the LPS-treated group compared to the control group, and LPS plus osmotin-treated mice exhibited an increased expression of SNAP-25 and PSD-95 compared to the LPS-treated group (Fig. 6B).


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 synaptic dysfunction and memory impairment.(A) Shown are representative Western blots probed with PSD-95, SNAP-25, SYP, and syntaxin-1 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 analysis of PSD-95- and SNAP-25-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 hippocampus show PSD-95- and SNAP-25-stained brain tissue at a magnification of 10x objective field, scale bar = 50 μm. Symbols for treatment groups and level of significance are mentioned in the data analysis section of the Materials and Methods. (C) Behavioral studies show osmotin improves memory impairment in LPS-treated mice (n = 5 per group). (a) Average escape latency time for experimental mice to reach the hidden platform from day 3 to day 8. (b) The number of crossings at the hidden platform during the probe test of the Morris water maze experiment. (c) Time spent in the platform quadrant, where the hidden platform was placed during the trial session. Symbols for treatment groups and levels of significance are mentioned in the data analysis section of the Materials and Methods.
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Related In: Results  -  Collection

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f6: Effect of osmotin on LPS-induced synaptic dysfunction and memory impairment.(A) Shown are representative Western blots probed with PSD-95, SNAP-25, SYP, and syntaxin-1 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 analysis of PSD-95- and SNAP-25-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 hippocampus show PSD-95- and SNAP-25-stained brain tissue at a magnification of 10x objective field, scale bar = 50 μm. Symbols for treatment groups and level of significance are mentioned in the data analysis section of the Materials and Methods. (C) Behavioral studies show osmotin improves memory impairment in LPS-treated mice (n = 5 per group). (a) Average escape latency time for experimental mice to reach the hidden platform from day 3 to day 8. (b) The number of crossings at the hidden platform during the probe test of the Morris water maze experiment. (c) Time spent in the platform quadrant, where the hidden platform was placed during the trial session. Symbols for treatment groups and levels of significance are mentioned in the data analysis section of the Materials and Methods.
Mentions: Recent studies demonstrated that disruption of synaptic function is a primary feature of AD and causes cognitive dysfunction and memory impairment with or without the induction of neurodegeneration31. Therefore, we investigated the effect of LPS and osmotin on postsynaptic (PSD-95) and presynaptic proteins, such as synaptophysin (SYP), synaptosomal associated protein (SNAP-25), and syntaxin-1. Western blot analyses revealed that systemic LPS administration decreased protein levels of PSD-95, SYP, SNAP-25, and syntaxin-1 in the hippocampus of adult mice compared to the control group. Osmotin treatment reversed the LPS-induced effect on synaptic markers and increased the expression of PSD-95, SYP, SNAP-25, and syntaxin-1 compared to the LPS-treated group (Fig. 6A). Immunofluorescence analyses also demonstrated the protective effect of osmotin on LPS-induced synaptic dysfunction. Confocal microscopy revealed a decrease in the fluorescence signals of SNAP-25 and PSD-95 in the hippocampus of the LPS-treated group compared to the control group, and LPS plus osmotin-treated mice exhibited an increased expression of SNAP-25 and PSD-95 compared to the LPS-treated group (Fig. 6B).

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