Cognitive benefits of lithium chloride in APP/PS1 mice are associated with enhanced brain clearance of β-amyloid

Pan, Yijun; Short, Jennifer Lynn; Newman, Stephanie A; Choy, Kwok Ho Christopher; Tiwari, Durgesh; Yap, Cheng‐Hon; Senyschyn, Danielle; Banks, William A.; Nicolazzo, Joseph A.

doi:10.1016/j.bbi.2018.03.007

Cited by 42 publications

(42 citation statements)

References 65 publications

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“…Therefore, we observed the effect of Rg1 treatment on APP/PS1 mice from 6M to 9M in the present study. In this study, the behavior results indicated that the APP/PS1-6M mice showed an increase of hyperactivity in the open eld test (OFT) which also reported in other studies [44] and slight impairments of learning and memory in Morris water maze (MWM) test. But the APP/PS1-9M mice showed signi cant hyperactivity and learning and memory impairments compared with WT-9M group.…”

Section: Discussionsupporting

confidence: 85%

Ginsenoside Rg1 alleviates Aβ deposition and neuronal damage by inhibiting NLRP1 inflammasome activation in APP/PS1 mice

Zhang¹,

Su²,

Sun³

et al. 2020

Preprint

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Background: Oxidative stress and neuroinflammation play important roles in the whole pathogenesis of Alzheimer's disease (AD). NADPH oxidase 2 (NOX2) is an important enzyme that is responsible for ROS generation in many neurodegenerative diseases. The nucleotide-binding oligomerization domain (NOD)-like receptor protein 1 (NLRP1) inflammasome is responsible for the formation of pro-inflammatory molecules in neurons. However, it is still unclear whether inhibition of NOX2 and NLRP1 inflammasome decreases amyloid-beta (Aβ) generation and deposition in APP/PS1 mice. Ginsenoside Rg1 (Rg1) is an active component in ginseng, and maybe a potential agent for neurodegenerative diseases. In this study, we investigated the effects and mechanisms of Rg1 treatment on cognitive performance, neuronal damage, Aβ deposition and NOX2-NLRP1 inflammasome activation in APP/PS1 mice.Methods: WT and APP/PS1 mice were used in the experiment from 6 months (M) old to 9M old, and 6M APP/PS1 mice were used as pre-treatment controls. The open field test (OFT) and Morris water maze (MWM) were used to detect behavioral change and cognitive function. The H&E and Nissl staining were used to assess neuronal damage. We further examined PSD95 expression, Aβ generation and deposition, Tau and p-Tau expression, NOX2-mediated ROS generation and NLRP1 inflammasome activation by using immunofluorescence, western blot analysis, and real time q-PCR.Results: Rg1 treatment for 12 weeks alleviated learning and memory impairments and neuronal damage, decreased p-Tau level, APP expression and Aβ deposition in APP/PS1 mice. Meanwhile, Rg1 treatment significantly decreased the levels of ROS and IL-1β, and reduced the expressions of NOX2 and NLRP1 inflammasome in the brain cortex and hippocampus in APP/PS1 mice. Furthermore, apocynin (a NOX inhibitor) and NLRP1-siRNA treatment also alleviated cognitive impairments, neuronal damage and Aβ deposition, and reduced the expression of NLRP1 inflammasome in brain cortex and hippocampus in APP/PS1 mice.Conclusions: Rg1 treatment could alleviate learning and memory impairment, neuronal damage, and reduce Aβ generation and deposition by inhibiting NLRP1 inflammasome activation in APP/PS1 mice.

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Section: Discussionsupporting

confidence: 85%

Ginsenoside Rg1 alleviates Aβ deposition and neuronal damage by inhibiting NLRP1 inflammasome activation in APP/PS1 mice

Zhang¹,

Su²,

Sun³

et al. 2020

Preprint

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“…Aβ levels were upregulated early in the progression of AD, and this change was strongly correlated with a decline in cognitive function ( Pan et al, 2018 ). Studies have shown that knockout of the miR132 gene in AD transgenic mice results in impaired memory and increased Aβ expression ( Min et al, 2010 ).…”

Section: Resultsmentioning

confidence: 99%

Intranasal Delivery of Targeted Nanoparticles Loaded With miR-132 to Brain for the Treatment of Neurodegenerative Diseases

Sun

Gao

et al. 2020

Front. Pharmacol.

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Effective treatments for neurodegenerative diseases need to be developed. MiR132 is abundantly expressed in the brain, and it modulates neuron morphology and plays a key role in maintaining neuron survival. Regulating miR132 can effectively improve the symptoms of Alzheimer's disease. It can also reduce cell death after cerebral hemorrhage, improve the microenvironment of hematoma lesions and provide a certain protective effect from brain damage after cerebral ischemia. MiR132 has great potential in the treatment of cerebral ischemia and Alzheimer's disease. To prevent the decline of miR132 of miR132 levels in the blood, we used mouse and rat models of Alzheimer's disease with ischemic brain injury, and then delivered Wheat germ agglutinin (WGA)-NPs-miR132 intranasally to treat neurological damage after cerebral ischemia. Synaptic protein expression levels in Alzheimer's mouse models increased significantly after administration. We propose that, nasal delivery of WGA-NPs-miR132 is an interesting novel therapeutic approach for the treatment of neurodegenerative diseases.

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“…In the AD patients, senile plaques can be detected in the brain. 16 Ab is the main constituent of the senile plaques, the Ab plaque and protein in the AD mice fed in EE were significantly reduced, indicating that the course of the disease in AD mice has been alleviated.…”

Section: Discussionmentioning

confidence: 98%

The short-term improvements of enriched environment in behaviors and pathological changes of APP/PS1 mice via regulating cytokines

Zhang

Wang

et al. 2018

Human Vaccines & Immunotherapeutics

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Cognitive benefits of lithium chloride in APP/PS1 mice are associated with enhanced brain clearance of β-amyloid

Cited by 42 publications

References 65 publications

Ginsenoside Rg1 alleviates Aβ deposition and neuronal damage by inhibiting NLRP1 inflammasome activation in APP/PS1 mice

Ginsenoside Rg1 alleviates Aβ deposition and neuronal damage by inhibiting NLRP1 inflammasome activation in APP/PS1 mice

Intranasal Delivery of Targeted Nanoparticles Loaded With miR-132 to Brain for the Treatment of Neurodegenerative Diseases

The short-term improvements of enriched environment in behaviors and pathological changes of APP/PS1 mice via regulating cytokines

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