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NLRC3 delays the progression of AD in APP/PS1 mice via inhibiting PI3K activation
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Abstract
Background/Aims: NLRC3 inhibits inflammatory responses. Epidemiological studies indicate that neuroinflammation induces and accelerates the onset of Alzheimer's disease (AD). This study was designed to determine whether NLRC3 plays a role in neuroinflammation, Aβ accumulation and neuroprotection in AD mice. Methods: Thirty 12-month-old APP/PS1 transgenic mice were randomized into three groups as model group, APP/PS1 +LVCON307 and APP/PS1 +LV-NLRC3 group. Ten 12-month-old wild-type C57 mice were chosen as control group. Mice in APP/PS1 +LVCON307 and APP/PS1 +LV-NLRC3 group were injected with LVCON307 or LV-NLRC3 through intracerebroventricular injection. Six months after LVCON307 or LV-NLRC3 injection, We carried out Morris water maze test on mice and harvested their brain tissues after the behavioral experiment. The deposition of amyloid protein and the changes of Nissle bodies were observed by ThS and Nissle staining. The expressions of NLRC3, 6E10, GFAP, Iba1, NeuN and PI3K were detected by immunohistochemistry or immunofluorescence. Western blot was used to analyze the expression of NLRC3, PI3K, GFAP and Iba1. Results: The expression of NLRC3 is down-regulated in brain tissues of APP/PS1 mice. Mice in APP/PS1 group had a significant attenuation of learning and memory ability compared to the control group, the ability of learning and memory was improved in APP/PS1 +LV-NLRC3 mice. The expression of 6E10, GFAP, Iba1 and PI3K in brain and hippocampus slice of APP/PS1 and APP/PS1 + LVCON307 mice were significantly higher than those of the control group, while the expression of NLRC3 and NeuN was significantly lower than that of the control group. After overexpression of NLRC3, the expression of 6e10, GFAP, Iba1 and PI3K in APP/PS1 + LV-NLRC3 group was significantly lower than that in APP/PS1 and APP/PS1 + LVCON307 group, while the expression of NLRC3 and NeuN was significantly higher than that in APP/PS1 and APP/PS1 + LVCON307 group. NLRC3 co-localized with NeuN. PI3K activation with 740YP increased the expression of GFAP and Iba-1 in hippocampus with exogenous NLRC3 protein. Conclusion: NLRC3 may play an important role in the development and progression of AD. Down-regulation of NLRC3 can lead to the activation of PI3K, resulting in abnormal plaque deposition, glial cell activation and neuron loss during AD. NLRC3 delays the progression of AD in APP/PS1 mice via inhibiting PI3K activation. Keywords: NLRC3 • inflammation • Aβ • neuron •PI3K •Alzheimer's disease
Springer Science and Business Media LLC
Title: NLRC3 delays the progression of AD in APP/PS1 mice via inhibiting PI3K activation
Description:
Abstract
Background/Aims: NLRC3 inhibits inflammatory responses.
Epidemiological studies indicate that neuroinflammation induces and accelerates the onset of Alzheimer's disease (AD).
This study was designed to determine whether NLRC3 plays a role in neuroinflammation, Aβ accumulation and neuroprotection in AD mice.
Methods: Thirty 12-month-old APP/PS1 transgenic mice were randomized into three groups as model group, APP/PS1 +LVCON307 and APP/PS1 +LV-NLRC3 group.
Ten 12-month-old wild-type C57 mice were chosen as control group.
Mice in APP/PS1 +LVCON307 and APP/PS1 +LV-NLRC3 group were injected with LVCON307 or LV-NLRC3 through intracerebroventricular injection.
Six months after LVCON307 or LV-NLRC3 injection, We carried out Morris water maze test on mice and harvested their brain tissues after the behavioral experiment.
The deposition of amyloid protein and the changes of Nissle bodies were observed by ThS and Nissle staining.
The expressions of NLRC3, 6E10, GFAP, Iba1, NeuN and PI3K were detected by immunohistochemistry or immunofluorescence.
Western blot was used to analyze the expression of NLRC3, PI3K, GFAP and Iba1.
Results: The expression of NLRC3 is down-regulated in brain tissues of APP/PS1 mice.
Mice in APP/PS1 group had a significant attenuation of learning and memory ability compared to the control group, the ability of learning and memory was improved in APP/PS1 +LV-NLRC3 mice.
The expression of 6E10, GFAP, Iba1 and PI3K in brain and hippocampus slice of APP/PS1 and APP/PS1 + LVCON307 mice were significantly higher than those of the control group, while the expression of NLRC3 and NeuN was significantly lower than that of the control group.
After overexpression of NLRC3, the expression of 6e10, GFAP, Iba1 and PI3K in APP/PS1 + LV-NLRC3 group was significantly lower than that in APP/PS1 and APP/PS1 + LVCON307 group, while the expression of NLRC3 and NeuN was significantly higher than that in APP/PS1 and APP/PS1 + LVCON307 group.
NLRC3 co-localized with NeuN.
PI3K activation with 740YP increased the expression of GFAP and Iba-1 in hippocampus with exogenous NLRC3 protein.
Conclusion: NLRC3 may play an important role in the development and progression of AD.
Down-regulation of NLRC3 can lead to the activation of PI3K, resulting in abnormal plaque deposition, glial cell activation and neuron loss during AD.
NLRC3 delays the progression of AD in APP/PS1 mice via inhibiting PI3K activation.
Keywords: NLRC3 • inflammation • Aβ • neuron •PI3K •Alzheimer's disease.
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