scholarly journals Systemic Exposure to Lipopolysaccharide from Porphyromonas gingivalis Induces Bone Loss-Correlated Alzheimer’s Disease-Like Pathologies in Middle-Aged Mice

2020 ◽  
Vol 78 (1) ◽  
pp. 61-74
Author(s):  
Yebo Gu ◽  
Zhou Wu ◽  
Fan Zeng ◽  
Muzhou Jiang ◽  
Jessica L. Teeling ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Bone Loss ◽  
Porphyromonas Gingivalis ◽  
Specific Inhibitor ◽  
Systemic Exposure ◽  
Memory Decline ◽  
Periodontal Bacteria ◽  
Pre Treatment ◽  
Total Tissue

Background: Alzheimer’s disease (AD) and bone loss are clinically exacerbated. However, the mechanism of exacerbation remains understood. Objective: We tested our hypothesis that periodontitis is involved in the exacerbation, contributing to AD pathologies. Methods: The bone, memory, and inflammation in bone and brain were examined in 12-month-old mice after systemic exposure to lipopolysaccharide from Porphyromonas gingivalis (P gLPS) for 3 consecutive weeks. Results: Compared with control mice, bone loss in tibia (26% decrease) and memory decline (47% decrease) were induced in mice with a positive correlation after exposure to P gLPS (r = 0.7378, p = 0.0011). The IL-6 and IL-17 expression in tibia was negatively correlated with the bone volume/total tissue volume (r = –0.6619, p = 0.0052; r = –0.7129, p = 0.0019), while that in the cortex was negatively correlated with the memory test latency (r = –0.7198, p = 0.0017; p = 0.0351, r = –0.5291). Furthermore, the IL-17 expression in microglia was positively correlated with Aβ42 accumulation in neurons (r = 0.8635, p < 0.0001). In cultured MG6 microglia, the P gLPS-increased IL-6 expression was inhibited by a PI3K-specific inhibitor (68% decrease), and that of IL-17 was inhibited by IL-6 antibody (41% decrease). In cultured N2a neurons, conditioned medium from P gLPS-stimulated microglia (MCM) but not P gLPS increased the productions of AβPP, CatB, and Aβ42, which were significantly inhibited by pre-treatment with IL-17 antibody (67%, 51%, and 41% decrease). Conclusion: These findings demonstrated that chronic systemic exposure to P gLPS simultaneously induces inflammation-dependent bone loss and AD-like pathologies by elevating IL-6 and IL-17 from middle age, suggesting that periodontal bacteria induce exacerbation of bone loss and memory decline, resulting in AD progression.

Porphyromonas Gingivalis Infection Induces Synaptic Failure via Increased IL-1β Production in Leptomeningeal Cells

2021 ◽  
pp. 1-17
Author(s):  
Wanyi Huang ◽  
Fan Zeng ◽  
Yebo Gu ◽  
Muzhou Jiang ◽  
Xinwen Zhang ◽  
...  
Keyword(s):  
Porphyromonas Gingivalis ◽  
Nlrp3 Inflammasome ◽  
Cortical Neurons ◽  
Inflammasome Activation ◽  
Memory Decline ◽  
Periodontal Bacteria ◽  
Nlrp3 Inflammasome Activation ◽  
Synaptic Failure ◽  
Pre Treatment ◽  
The Impact

Background: Studies have reported that synaptic failure occurs before the Alzheimer’s disease (AD) onset. The systemic Porphyromonas gingivalis (P. gingivalis) infection is involved in memory decline. We previously showed that leptomeningeal cells, covering the brain, activate glial cells by releasing IL-1β in response to systemic inflammation. Objective: In the present study, we focused on the impact of leptomeningeal cells on neurons during systemic P. gingivalis infection. Methods: The responses of leptomeningeal cells and cortical neurons to systemic P. gingivalis infection were examined in 15-month-old mice. The mechanism of IL-1β production by P. gingivalis infected leptomeningeal cells was examined, and primary cortical neurons were treated with P. gingivalis infected leptomeningeal cells condition medium (Pg LCM). Results: Systemic P. gingivalis infection increased the expression of IL-1β in leptomeninges and reduced the synaptophysin (SYP) expression in leptomeninges proximity cortex in mice. Leptomeningeal cells phagocytosed P. gingivalis resulting in lysosomal rupture and Cathepsin B (CatB) leakage. Leaked CatB mediated NLRP3 inflammasome activation inducing IL-1β secretion in leptomeningeal cells. Pg LCM decreased the expression of synaptic molecules, including SYP, which was inhibited by an IL-1 receptor antagonist pre-treatment. Conclusion: These observations demonstrate that P. gingivalis infection is involved in synaptic failure by inducing CatB/NLRP3 inflammasome-mediated IL-1β production in leptomeningeal cells. The periodontal bacteria-induced synaptic damage may accelerate the onset and cognitive decline of AD.

scholarly journals 24(S)-Saringosterol Prevents Cognitive Decline in a Mouse Model for Alzheimer’s Disease

Marine Drugs ◽  
2021 ◽  
Vol 19 (4) ◽  
pp. 190
Author(s):  
Nikita Martens ◽  
Melissa Schepers ◽  
Na Zhan ◽  
Frank Leijten ◽  
Gardi Voortman ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Cognitive Decline ◽  
Inflammatory Marker ◽  
Amyloid Β ◽  
Liver Fat ◽  
Gas Chromatography Mass Spectrometry ◽  
Memory Decline ◽  
Plaque Load

We recently found that dietary supplementation with the seaweed Sargassum fusiforme, containing the preferential LXRβ-agonist 24(S)-saringosterol, prevented memory decline and reduced amyloid-β (Aβ) deposition in an Alzheimer’s disease (AD) mouse model without inducing hepatic steatosis. Here, we examined the effects of 24(S)-saringosterol as a food additive on cognition and neuropathology in AD mice. Six-month-old male APPswePS1ΔE9 mice and wildtype C57BL/6J littermates received 24(S)-saringosterol (0.5 mg/25 g body weight/day) (APPswePS1ΔE9 n = 20; C57BL/6J n = 19) or vehicle (APPswePS1ΔE9 n = 17; C57BL/6J n = 19) for 10 weeks. Cognition was assessed using object recognition and object location tasks. Sterols were analyzed by gas chromatography/mass spectrometry, Aβ and inflammatory markers by immunohistochemistry, and gene expression by quantitative real-time PCR. Hepatic lipids were quantified after Oil-Red-O staining. Administration of 24(S)-saringosterol prevented cognitive decline in APPswePS1ΔE9 mice without affecting the Aβ plaque load. Moreover, 24(S)-saringosterol prevented the increase in the inflammatory marker Iba1 in the cortex of APPswePS1ΔE9 mice (p < 0.001). Furthermore, 24(S)-saringosterol did not affect the expression of lipid metabolism-related LXR-response genes in the hippocampus nor the hepatic neutral lipid content. Thus, administration of 24(S)-saringosterol prevented cognitive decline in APPswePS1ΔE9 mice independent of effects on Aβ load and without adverse effects on liver fat content. The anti-inflammatory effects of 24(S)-saringosterol may contribute to the prevention of cognitive decline.

Plasma cortisol and norepinephrine in Alzheimer’s disease: opposite relations with recall performance and stage of progression

2007 ◽  
Vol 19 (4) ◽  
pp. 231-237 ◽  
Author(s):  
Karel J. Bemelmans ◽  
Annemarie Noort ◽  
Roel de Rijk ◽  
Huub A. M. Middelkoop ◽  
Godfried M. J. van Kempen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Hippocampal Neurons ◽  
Plasma Cortisol ◽  
Recall Performance ◽  
Area Under The Curve ◽  
Plasma Norepinephrine ◽  
Clinical Dementia Rating ◽  
Memory Decline ◽  
Word Lists

Objective:Alzheimer’s disease (AD) is characterized by effortful retrieval memory impairments, loss of hippocampal neurons and elevated plasma cortisol (CORT) concentrations. The latter could induce further memory decline. AD is also characterized by increased central and peripheral noradrenergic activity. Since noradrenergic function is involved in memory formation, this upregulated function could counteract memory decline. The aim of the present study was to test these hypotheses using plasma norepinephrine (NE) as a noradrenergic parameter, and recall of the prerecency part of neutral valence word lists as a measure of effortful retrieval.Methods:Area under the curve (AUC) of morning, midday and afternoon plasma CORT and plasma NE concentrations was related to two measures of recall performance, ie summated recall scores of the prerecency and recency parts of three word lists, and to the stage of the Clinical Dementia Rating (CDR).Results:Partial correlation between each hormone AUC value and prerecency recall performance, controlling for the effect of the other hormone, showed opposite relations between recall and either plasma CORT or NE. Similar stronger correlations were found with the CDR score.Conclusions:Plasma CORT and NE are oppositely related with effortful retrieval and the stage of progression in AD.

Rosiglitazone reverses memory decline and hippocampal glucocorticoid receptor down-regulation in an Alzheimer’s disease mouse model

2009 ◽  
Vol 379 (2) ◽  
pp. 406-410 ◽  
Author(s):  
Luis Escribano ◽  
Ana-María Simón ◽  
Alberto Pérez-Mediavilla ◽  
Pablo Salazar-Colocho ◽  
Joaquín Del Río ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Glucocorticoid Receptor ◽  
Down Regulation ◽  
Memory Decline

scholarly journals Therapeutic potential of astaxanthin and superoxide dismutase in Alzheimer's disease

Open Biology ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 210013
Author(s):  
Vyshnavy Balendra ◽  
Sandeep Kumar Singh
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Superoxide Dismutase ◽  
Antioxidant System ◽  
Tau Protein ◽  
Therapeutic Potential ◽  
Plaque Burden ◽  
Memory Decline ◽  
Endogenous Antioxidants ◽  
The Brain

Oxidative stress, the imbalance of the antioxidant system, results in an accumulation of neurotoxic proteins in Alzheimer's disease (AD). The antioxidant system is composed of exogenous and endogenous antioxidants to maintain homeostasis. Superoxide dismutase (SOD) is an endogenous enzymatic antioxidant that converts superoxide ions to hydrogen peroxide in cells. SOD supplementation in mice prevented cognitive decline in stress-induced cells by reducing lipid peroxidation and maintaining neurogenesis in the hippocampus. Furthermore, SOD decreased expression of BACE1 while reducing plaque burden in the brain. Additionally, Astaxanthin (AST), a potent exogenous carotenoid, scavenges superoxide anion radicals. Mice treated with AST showed slower memory decline and decreased depositions of amyloid-beta (A β ) and tau protein. Currently, the neuroprotective potential of these supplements has only been examined separately in studies. However, a single antioxidant cannot sufficiently resist oxidative damage to the brain, therefore, a combinatory approach is proposed as a relevant therapy for ameliorating pathological changes in AD.

scholarly journals Hippocampal proteomics defines pathways associated with memory decline and resilience in normal aging and Alzheimer’s disease mouse models

2017 ◽  
Vol 322 ◽  
pp. 288-298 ◽  
Author(s):  
Sarah M. Neuner ◽  
Lynda A. Wilmott ◽  
Brian R. Hoffmann ◽  
Khyobeni Mozhui ◽  
Catherine C. Kaczorowski
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Models ◽  
Normal Aging ◽  
Memory Decline ◽  
With Memory

ODor-evoked Autobiographical Memory in Alzheimer’s disease?

2021 ◽  
Author(s):  
Mohamad El Haj
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Autobiographical Memory ◽  
Personal Information ◽  
Disease Model ◽  
Olfactory Stimulation ◽  
Autobiographical Memories ◽  
Comprehensive Overview ◽  
Memory Decline ◽  
Stimulation Of

Abstract Objective Because memory decline is the hallmark of Alzheimer’s disease (AD), an important endeavor for both clinicians and researchers is to improve memory performances in AD. This can be pursued by olfactory stimulation of memory in patients with AD and by studying the effects of olfactory stimulation on autobiographical memory (i.e., memory for personal information). The effects of olfactory stimulation on autobiographical memory in patients with mild AD have been reported by recent research. We thus provide the first comprehensive overview of research on odor-evoked autobiographical memory in AD. We also establish the basis for solid theoretical analysis concerning the memory improvement reported by research on odor-evoked autobiographical memory in AD. Method We examined literature on odor-evoked autobiographical memories in AD and propose the “OdAMA” (Odor-evoked Autobiographical Memory in Alzheimer’s disease) model. Results and discussion According to OdAMA model, odor exposure activates involuntary access to specific autobiographical memories, which promotes enhanced experience subjective of retrieval in patients with AD and improves their ability to construct not only recent and remote events but also future ones. The OdAMA model could serve as a guide for researchers and clinicians interested in odor-evoked autobiographical memory in AD.

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