Tooth Loss Induces Memory Impairment and Gliosis in App Knock-In Mouse Models of Alzheimer’s Disease

2021 ◽  
Vol 80 (4) ◽  
pp. 1687-1704
Author(s):  
Ferdous Taslima ◽  
Cha-Gyun Jung ◽  
Chunyu Zhou ◽  
Mona Abdelhamid ◽  
Mohammad Abdullah ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mrna Expression ◽  
Neuronal Activity ◽  
Memory Impairment ◽  
Tooth Loss ◽  
Amyloid Β ◽  
Glial Activation ◽  
Expression Levels ◽  
Mrna Expression Levels

Background: Epidemiological studies have shown that tooth loss is associated with Alzheimer’s disease (AD) and dementia. However, the molecular and cellular mechanisms by which tooth loss causes AD remain unclear. Objective: We investigated the effects of tooth loss on memory impairment and AD pathogenesis in AppNL-G-F mice. Methods: Maxillary molar teeth on both sides were extracted from 2-month-old AppNL-G-F mice, and the mice were reared for 2 months. The short- and long-term memory functions were evaluated using a novel object recognition test and a passive avoidance test. Amyloid plaques, amyloid-β (Aβ) levels, glial activity, and neuronal activity were evaluated by immunohistochemistry, Aβ ELISA, immunofluorescence staining, and western blotting. The mRNA expression levels of neuroinflammatory cytokines were determined by qRT-PCR analysis. Results: Tooth loss induced memory impairment via an amyloid-cascade-independent pathway, and decreased the neuronal activity, presynaptic and postsynaptic protein levels in both the cortex and hippocampus. Interestingly, we found that tooth loss induced glial activation, which in turn leads to the upregulation of the mRNA expression levels of the neuroinflammation cytokines tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and IL-1β in the hippocampus. We also found that tooth loss activated a stress-activated protein kinase, c-Jun N-terminal kinase (JNK), and increased heat shock protein 90 (HSP90) levels in the hippocampus, which may lead to a glial activation. Conclusion: Our findings suggest that taking care of teeth is very important to preserve a healthy oral environment, which may reduce the risk of cognitive dysfunction.

scholarly journals Metformin Ameliorates Aβ Pathology by Insulin-Degrading Enzyme in a Transgenic Mouse Model of Alzheimer’s Disease

2020 ◽  
Vol 2020 ◽  
pp. 1-10 ◽  
Author(s):  
Xin-Yi Lu ◽  
Shun Huang ◽  
Qu-Bo Chen ◽  
Dapeng Zhang ◽  
Wanyan Li ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Transgenic Mice ◽  
Mrna Expression ◽  
Insulin Degrading Enzyme ◽  
Antidiabetic Drug ◽  
Degrading Enzyme ◽  
Expression Levels ◽  
The Brain ◽  
Mrna Expression Levels

Alzheimer’s disease (AD) is the most common neurodegenerative disease. The accumulation of amyloid beta (Aβ) is the main pathology of AD. Metformin, a well-known antidiabetic drug, has been reported to have AD-protective effect. However, the mechanism is still unclear. In this study, we tried to figure out whether metformin could activate insulin-degrading enzyme (IDE) to ameliorate Aβ-induced pathology. Morris water maze and Y-maze results indicated that metformin could improve the learning and memory ability in APPswe/PS1dE9 (APP/PS1) transgenic mice. 18F-FDG PET-CT result showed that metformin could ameliorate the neural dysfunction in APP/PS1 transgenic mice. PCR analysis showed that metformin could effectively improve the mRNA expression level of nerve and synapse-related genes (Syp, Ngf, and Bdnf) in the brain. Metformin decreased oxidative stress (malondialdehyde and superoxide dismutase) and neuroinflammation (IL-1β and IL-6) in APP/PS1 mice. In addition, metformin obviously reduced the Aβ level in the brain of APP/PS1 mice. Metformin did not affect the enzyme activities and mRNA expression levels of Aβ-related secretases (ADAM10, BACE1, and PS1). Meanwhile, metformin also did not affect the mRNA expression levels of Aβ-related transporters (LRP1 and RAGE). Metformin increased the protein levels of p-AMPK and IDE in the brain of APP/PS1 mice, which might be the key mechanism of metformin on AD. In conclusion, the well-known antidiabetic drug, metformin, could be a promising drug for AD treatment.

scholarly journals Probiotic Bifidobacterium breve Prevents Memory Impairment Through the Reduction of Both Amyloid-β Production and Microglia Activation in APP Knock-In Mouse

2021 ◽  
pp. 1-17
Author(s):  
Mona Abdelhamid ◽  
Chunyu Zhou ◽  
Kazuya Ohno ◽  
Tetsuya Kuhara ◽  
Ferdous Taslima ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Inflammatory Cytokines ◽  
Memory Impairment ◽  
Molecular Mechanisms ◽  
Amyloid Β ◽  
Synaptic Proteins ◽  
Amyloid Β Protein ◽  
Bifidobacterium Breve ◽  
Expression Levels ◽  
Mrna Expression Levels

Background: Probiotic supplementation reestablishes microbiome diversity and improves brain function in Alzheimer’s disease (AD); their molecular mechanisms, however, have not yet been fully illustrated. Objective: We investigated the effects of orally supplemented Bifidobacterium breve MCC1274 on cognitive function and AD-like pathologies in AppNL-G-F mice. Methods: Three-month-old AppNL-G-F mice were orally supplemented with B. breve MCC1274 for four months. The short-term memory function was evaluated using a novel object recognition test. Amyloid plaques, amyloid-β (Aβ) levels, Aβ fibril, amyloid-β protein precursor and its processing enzymes, its metabolic products, glial activity, and cell proliferation in the subgranular zone of the dentate gyrus were evaluated by immunohistochemistry, Aβ ELISA, western blotting, and immunofluorescence staining. The mRNA expression levels of pro- and anti-inflammatory cytokines were determined by qRT-PCR analysis. Results: We found that the oral B. breve MCC1 274 supplementation prevented memory impairment in AppNL-G-F mice and decreased hippocampal Aβ levels through the enhancement of the a-disintegrin and metalloproteinase 10 (ADAM10) level. Moreover, administration of the probiotic activated the ERK/HIF-1α signaling pathway responsible for increasing the ADAM10 level and also attenuated microglial activation, which in turn led to reduction in the mRNA expression levels of pro-inflammatory cytokines in the brain. In addition, B. breve MCC1274 supplementation increased the level of synaptic proteins in the hippocampus. Conclusion: Our findings support the possibility that oral B. breve MCC1274 supplementation might be used as a potential preventive therapy for AD progression.

Effect of Bee Venom on an Experimental Cellular Model of Alzheimer’s Disease

2020 ◽  
Vol 48 (08) ◽  
pp. 1803-1819
Author(s):  
Yong Ho Ku ◽  
Jae Hui Kang ◽  
Hyun Lee
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mrna Expression ◽  
Caspase 3 ◽  
Bee Venom ◽  
Control Group ◽  
Cellular Model ◽  
Expression Levels ◽  
Cox 2 ◽  
Mrna Expression Levels

Alzheimer’s disease (AD) is a neurodegenerative disease and is characterized by the deposition of the [Formula: see text]-Amyloid peptide ([Formula: see text]A), which causes the inflammation of neurons. Bee venom (BV) elicits a strong anti-inflammatory response, and therefore we conducted an in vitro experiment to study the efficacy of BV in an AD cellular model. To mimic AD, the U87MG cell line was incubated for 168 hours with 2.5 [Formula: see text]M [Formula: see text]A. Changes were confirmed by microscopy, and peptides were measured under stain-free conditions using homo-tomography. Sulforhodamine B analysis was performed to analyze the cell viability. Real-Time quantitative polymerase chain reaction (qPCR) analysis was conducted to analyze mRNA expression levels of pro-inflammatory cytokines (NF-[Formula: see text]B, COX-2, TNF-[Formula: see text], IL-1), and Western blot was performed to measure the Caspase-3 protein levels. BV showed no cytotoxicity at concentrations below 10 [Formula: see text]g/mL. The NF-[Formula: see text]B mRNA levels were not significantly different between the BV group and the control group. The amount of [Formula: see text]A accumulation in the BV group decreased significantly. The mRNA expression levels of COX-2, TNF-[Formula: see text], and IL-1 were significantly reduced using 10 [Formula: see text]g/mL of BV compared to those in the control group. Additionally, Caspase-3 levels were also reduced compared to those of the control group when BV was used at a concentration of 10 [Formula: see text]g/mL. BV could inhibit apoptosis and inflammatory responses in an AD cellular model. In addition, it prevented cell accumulation of [Formula: see text]A, an important pathogenic mechanism in AD.

scholarly journals RGS2 expression predicts amyloid-β sensitivity, MCI and Alzheimer’s disease: genome-wide transcriptomic profiling and bioinformatics data mining

2016 ◽  
Vol 6 (10) ◽  
pp. e909-e909 ◽  
Author(s):  
A Hadar ◽  
E Milanesi ◽  
A Squassina ◽  
P Niola ◽  
C Chillotti ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Data Mining ◽  
Alzheimer's Disease ◽  
G Protein ◽  
Amyloid Β ◽  
Healthy Individuals ◽  
Transcriptomic Profiling ◽  
Expression Levels ◽  
Genome Wide ◽  
Lower Expression

Abstract Alzheimer's disease (AD) is the most frequent cause of dementia. Misfolded protein pathological hallmarks of AD are brain deposits of amyloid-β (Aβ) plaques and phosphorylated tau neurofibrillary tangles. However, doubts about the role of Aβ in AD pathology have been raised as Aβ is a common component of extracellular brain deposits found, also by in vivo imaging, in non-demented aged individuals. It has been suggested that some individuals are more prone to Aβ neurotoxicity and hence more likely to develop AD when aging brains start accumulating Aβ plaques. Here, we applied genome-wide transcriptomic profiling of lymphoblastoid cells lines (LCLs) from healthy individuals and AD patients for identifying genes that predict sensitivity to Aβ. Real-time PCR validation identified 3.78-fold lower expression of RGS2 (regulator of G-protein signaling 2; P=0.0085) in LCLs from healthy individuals exhibiting high vs low Aβ sensitivity. Furthermore, RGS2 showed 3.3-fold lower expression (P=0.0008) in AD LCLs compared with controls. Notably, RGS2 expression in AD LCLs correlated with the patients’ cognitive function. Lower RGS2 expression levels were also discovered in published expression data sets from postmortem AD brain tissues as well as in mild cognitive impairment and AD blood samples compared with controls. In conclusion, Aβ sensitivity phenotyping followed by transcriptomic profiling and published patient data mining identified reduced peripheral and brain expression levels of RGS2, a key regulator of G-protein-coupled receptor signaling and neuronal plasticity. RGS2 is suggested as a novel AD biomarker (alongside other genes) toward early AD detection and future disease modifying therapeutics.

Melatonin Attenuates Memory Impairment, Amyloid-β Accumulation, and Neurodegeneration in a Rat Model of Sporadic Alzheimer’s Disease

2015 ◽  
Vol 47 (1) ◽  
pp. 103-116 ◽  
Author(s):  
Ekaterina A. Rudnitskaya ◽  
Natalia A. Muraleva ◽  
Kseniya Yi. Maksimova ◽  
Elena Kiseleva ◽  
Nataliya G. Kolosova ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Rat Model ◽  
Memory Impairment ◽  
Amyloid Β ◽  
Sporadic Alzheimer’S Disease

scholarly journals Treadmill exercise improves memory and increases hippocampal BDNF in a rat model of Alzheimer's Disease

2020 ◽  
Vol 24 (4) ◽  
pp. 250-256
Author(s):  
Rokhsareh Abshenas ◽  
◽  
Tayebe Artimani ◽  
Iraj Amiri ◽  
Siamak Shahidi ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Avoidance Learning ◽  
Memory Impairment ◽  
Treadmill Exercise ◽  
Amyloid Β ◽  
Male Rats ◽  
Bdnf Expression ◽  
Learning Tasks ◽  
Model Of Alzheimer’S Disease

Introduction: Alzheimer’s disease is strongly correlated with learning and memory impairments. As exercise can enhance memory and learning, in this study, we have investigated the effects of treadmill exercise on memory impairment in amyloid β (Aβ)- treated rats focusing on brain-derived neurotrophic factor (BDNF) expression. Methods: Wistar male rats received intracerebroventricular (ICV) injection of Aβ and exercised on a treadmill for one month. Memory function was assessed using Morris water maze (MWM) and avoidance learning tasks. The level of BDNF was examined by the ELISA test. Results: The results of MWM and avoidance learning tasks showed that treadmill exercise could improve Aβ- induced memory impairment significantly. Moreover, BDNF expression increased following exercise in the Aβ- treated rats. Conclusion: The present results suggested that treadmill exercise may improve memory in Alzheimer’s disease by increasing BDNF level in the hippocampus.

scholarly journals Visuospatial memory impairment as a potential neurocognitive marker to predict tau pathology in Alzheimer’s continuum

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Eun Hyun Seo ◽  
Ho Jae Lim ◽  
Hyung-Jun Yoon ◽  
Kyu Yeong Choi ◽  
Jang Jae Lee ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Medial Temporal Lobe ◽  
Memory Impairment ◽  
Prediction Models ◽  
Characteristic Curve ◽  
Amyloid Β ◽  
Tau Pathology ◽  
Discrimination Ability

Abstract Background Given that tau accumulation, not amyloid-β (Aβ) burden, is more closely connected with cognitive impairment in Alzheimer’s disease (AD), a detailed understanding of the tau-related characteristics of cognitive function is critical in both clinical and research settings. We investigated the association between phosphorylated tau (p-Tau) level and cognitive impairment across the AD continuum and the mediating role of medial temporal lobe (MTL) atrophy. We also developed a prediction model for abnormal tau accumulation. Methods We included participants from the Gwangju Alzheimer’s Disease and Related Dementia Cohort in Korea, who completed cerebrospinal fluid analysis and clinical evaluation, and corresponded to one of three groups according to the biomarkers of A and T profiles based on the National Institute on Aging and Alzheimer’s Association research framework. Multiple linear and logistic regression analyses were performed to examine the association between p-Tau and cognition and to develop prediction models. Receiver operating characteristic curve analysis was performed to examine the discrimination ability of the models. Results Among 185 participants, 93 were classified as A-T-, 23 as A+T-, and 69 as A+T+. There was an association between decreased visuospatial delayed memory performance and p-Tau level (B = − 0.754, β = − 0.363, p < 0.001), independent of other relevant variables (e.g., Aβ). MTL neurodegeneration was found to mediate the association between the two. Prediction models with visuospatial delayed memory alone (area under the curve [AUC] = 0.872) and visuospatial delayed memory and entorhinal thickness (AUC = 0.921) for abnormal tau accumulation were suggested and they were validated in an independent sample (AUC = 0.879 and 0.891, respectively). Conclusion It is crucial to identify sensitive cognitive measures that capture subtle cognitive impairment associated with underlying pathological changes. Preliminary findings from the current study might suggest that abnormal tau accumulation underlies episodic memory impairment, particularly visuospatial modality, in the AD continuum. Suggested models are potentially useful in predicting tau pathology, and might be utilized practically in the field.

scholarly journals FcγRIIb mediates amyloid-β neurotoxicity and memory impairment in Alzheimer’s disease

2013 ◽  
Vol 123 (7) ◽  
pp. 2791-2802 ◽  
Author(s):  
Tae-In Kam ◽  
Sungmin Song ◽  
Youngdae Gwon ◽  
Hyejin Park ◽  
Ji-Jing Yan ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Memory Impairment ◽  
Amyloid Β
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