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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 attenuated LPS-induced apoptotic neurodegeneration in the hippocampus of adult mice (A) Shown are representative Western blots probed with caspase-3 and PARP-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). Shown are representative photomicrographs of (B) FJB staining (magnification 40× objective field, scale bar = 100 μm) and (C) Nissl staining (magnification 20× objective field, scale bar = 200 μm) for dead and damaged neurons. Images are representative of staining obtained in sections prepared from at least 5 animals per group. Symbols for treatment groups and level of significance are mentioned in the data analysis section of the Materials and Methods.
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f7: Osmotin attenuated LPS-induced apoptotic neurodegeneration in the hippocampus of adult mice (A) Shown are representative Western blots probed with caspase-3 and PARP-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). Shown are representative photomicrographs of (B) FJB staining (magnification 40× objective field, scale bar = 100 μm) and (C) Nissl staining (magnification 20× objective field, scale bar = 200 μm) for dead and damaged neurons. Images are representative of staining obtained in sections prepared from at least 5 animals per group. Symbols for treatment groups and level of significance are mentioned in the data analysis section of the Materials and Methods.

Mentions: Autocrine secretion of TNF-α and the increased production of NO are the predominant factors of LPS-induced apoptosis32. We investigated caspase-3 and PARP-1 protein expression to evaluate the effect of osmotin on LPS-induced apoptotic neurodegeneration. Caspase-3 is the primary executioner of apoptosis33, and PARP-1 overexpression induces DNA damage that is involved in the apoptotic pathway34. Our results demonstrated that osmotin administration significantly reduced LPS-induced elevated levels of caspase-3 and PARP-1, which supports its potential neuroprotective capability (Fig. 7A).


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

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

Osmotin attenuated LPS-induced apoptotic neurodegeneration in the hippocampus of adult mice (A) Shown are representative Western blots probed with caspase-3 and PARP-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). Shown are representative photomicrographs of (B) FJB staining (magnification 40× objective field, scale bar = 100 μm) and (C) Nissl staining (magnification 20× objective field, scale bar = 200 μm) for dead and damaged neurons. Images are representative of staining obtained in sections prepared from at least 5 animals per group. Symbols for treatment groups and level 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

f7: Osmotin attenuated LPS-induced apoptotic neurodegeneration in the hippocampus of adult mice (A) Shown are representative Western blots probed with caspase-3 and PARP-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). Shown are representative photomicrographs of (B) FJB staining (magnification 40× objective field, scale bar = 100 μm) and (C) Nissl staining (magnification 20× objective field, scale bar = 200 μm) for dead and damaged neurons. Images are representative of staining obtained in sections prepared from at least 5 animals per group. Symbols for treatment groups and level of significance are mentioned in the data analysis section of the Materials and Methods.
Mentions: Autocrine secretion of TNF-α and the increased production of NO are the predominant factors of LPS-induced apoptosis32. We investigated caspase-3 and PARP-1 protein expression to evaluate the effect of osmotin on LPS-induced apoptotic neurodegeneration. Caspase-3 is the primary executioner of apoptosis33, and PARP-1 overexpression induces DNA damage that is involved in the apoptotic pathway34. Our results demonstrated that osmotin administration significantly reduced LPS-induced elevated levels of caspase-3 and PARP-1, which supports its potential neuroprotective capability (Fig. 7A).

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