scholarly journals High Methionine Diet-Induced Alzheimer’s Disease like Symptoms Are Accompanied by 5-Methylcytosine Elevated Levels in the Brain

2021 ◽  
Vol 2021 ◽  
pp. 1-16
Author(s):  
Tingting Pi ◽  
Shenjiao Wei ◽  
Yongxuan Jiang ◽  
Jing-Shan Shi
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Food Intake ◽  
Amyloid Β ◽  
The Body ◽  
Morris Water Maze Test ◽  
Enzyme Linked Immunosorbent Assay ◽  
Ability Test ◽  
Maze Test ◽  
Related Proteins

Background. Excessive or insufficient intake of methionine (Met) causes neuronal dysfunction, neurodegeneration, cerebrovascular dysfunction, vascular leakage, and short-term memory loss, which result in the occurrence of Alzheimer’s disease- (AD-) like symptoms. Objective. To determine the relationship between high methionine diets (HMD) induced AD-like symptoms and 5-methylcytosine (5-mC) level. Methods. C57BL/6J mice were randomly divided into two groups: the control group (Maintain diets) and the model group (2% HMD). Mice were fed with 2% HMD for 9 weeks. Animals were weighed and food intake was recorded weekly. Open field test, nesting ability test, Y maze test, new object recognition test, and Morris water maze test were used to detect the motor, learning, and memory ability. Hematoxylin-eosin (HE) staining was used to observe the damage of cells in hippocampus and cortex. Immunofluorescence (IF) staining was used to detect the expression and distribution of amyloid-β 1-40 (Aβ1-40), amyloid-β 1-42 (Aβ1-42), and 5-methylcytosine (5-mC) in hippocampus and cortex. Western blotting (WB) was used to determine the expression of Aβ and DNA methyltransferases- (DNMTs-) related proteins in the cortex. Enzyme-linked immunosorbent assay (ELISA) was performed to detect homocysteine (Hcy) level (ELISA). Results. Feeding of HMD decreased the body weight and food intake of mice. Behavioral testing revealed that HMD caused learning, memory, and motor ability impairment in the mice. HE staining results showed that HMD feeding caused damage of hippocampal and cortical neurons, along with disordered cell arrangement, and loss of neurons. Furthermore, HMD increased the contents of Aβ1-40, Aβ1-42, and 5-mC in the hippocampus and cortex. WB results showed that HMD increased the expression of Aβ production-related proteins, such as amyloid precursor protein (APP) and beta-secretase 1 (BACE1), and decreased the expression of Aβ metabolism-related protein in the cortex, including insulin-degrading enzyme (IDE) and neprilysin (NEP). Additionally, the decreased expression of DNA methyltransferase1 (DNMT1) was observed in HMD-treated mice, but there was no significant change of DNMT3a level. ELISA results showed that HMD increased the levels of Hcy in serum. Conclusion. Our result suggested that the HMD can cause neurotoxicity, leading to AD-like symptoms in mice, which may be related to 5-mC elevated.

scholarly journals Lycopene-Loaded Microemulsion Regulates Neurogenesis in Rats with Aβ-Induced Alzheimer’s Disease Rats Based on the Wnt/β-catenin Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Wen-jing Ning ◽  
Ren-jun Lv ◽  
Ning Xu ◽  
Xun-yao Hou ◽  
Chao Shen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Β ◽  
Morris Water Maze Test ◽  
Spatial Learning And Memory ◽  
Pax6 Gene ◽  
Movement Trajectory ◽  
Gene Expressions ◽  
Qrt Pcr ◽  
Related Proteins

Objective. To investigate the effects of lycopene-loaded microemulsion (LME) on the cognitive function and neurogenesis in the dentate gyrus (DG) of the hippocampus and subventricular (SVZ) region of rats with amyloid β- (Aβ-) induced Alzheimer’s disease (AD) and its mechanism based on the Wnt/β-catenin pathway. Methods. Healthy Wistar rats were divided into four groups: the blank control (CON), AD control, traditional lycopene (LOO), and LME groups. The CON and AD groups were fed with normal saline, while the LOO group was fed with traditional lycopene, and the LME group was fed with lycopene-loaded microemulsion. Behavioral tests were performed after three weeks of gastric administration. Immunofluorescence-labeled cells were used to observe the differentiation and maturation of new nerve cells in the DG of the hippocampus and SVZ region. qRT-PCR and Western blotting detected the expression of neurogenesis genes and Wnt/β-catenin pathway-related proteins, respectively. Results. On the Morris water maze test, LME rats had significantly shortened movement trajectory on the searching platform, reduced escape latency time, and increased residence time on the original platform quadrant. In addition, more LME rats crossed the platform when it was removed. Thus, LME can improve the spatial learning and memory of Aβ-induced AD rats. On qRT-PCR, LME significantly increased Reelin, Nestin, and Pax6 gene expressions, which regulate neurogenesis. Immunofluorescence showed that LME could significantly increase BrdU+, Dcx+, BrdU+/Neun+, BrdU+/Dcx+ cells in the DG and SVZ regions, thus promoting neurogenesis. LME also reduced the number of Iba1+ and Iba1+/BrdU+ cells, thus reducing the neuroinflammatory response. On Western blot, LME upregulated the Wnt/β-catenin pathway by upregulating Wnt3a, β-catenin, Disheveled (Dvl), and p-GSK3β and downregulating p-β-catenin and GSK3β. Conclusion. LME attenuates cognitive impairment in Aβ-induced AD rats by promoting neurogenesis in the hippocampus and SVZ region through upregulating the Wnt/β-catenin pathway.

The Involvement of Post-Translational Modifications in Alzheimer's Disease

2018 ◽  
Vol 15 (4) ◽  
pp. 313-335 ◽  
Author(s):  
Serena Marcelli ◽  
Massimo Corbo ◽  
Filomena Iannuzzi ◽  
Lucia Negri ◽  
Fabio Blandini ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Protein Modification ◽  
Neurodegenerative Disorder ◽  
Amyloid Β ◽  
Normal Function ◽  
Ageing Population ◽  
Covalent Bonds ◽  
Post Translational Modifications ◽  
Related Proteins

Background: Alzheimer's disease (AD) is a neurodegenerative disorder recognized as the most common cause of chronic dementia among the ageing population. AD is histopathologically characterized by progressive loss of neurons and deposits of insoluble proteins, primarily composed of amyloid-β pelaques and neurofibrillary tangles (NFTs). Methods: Several molecular processes contribute to the formation of AD cellular hallmarks. Among them, post-translational modifications (PTMs) represent an attractive mechanism underlying the formation of covalent bonds between chemical groups/peptides to target proteins, which ultimately result modified in their function. Most of the proteins related to AD undergo PTMs. Several recent studies show that AD-related proteins like APP, Aβ, tau, BACE1 undergo post-translational modifications. The effect of PTMs contributes to the normal function of cells, although aberrant protein modification, which may depend on many factors, can drive the onset or support the development of AD. Results: Here we will discuss the effect of several PTMs on the functionality of AD-related proteins potentially contributing to the development of AD pathology. Conclusion: We will consider the role of Ubiquitination, Phosphorylation, SUMOylation, Acetylation and Nitrosylation on specific AD-related proteins and, more interestingly, the possible interactions that may occur between such different PTMs.

scholarly journals Musical Electroacupuncture May Be a Better Choice than Electroacupuncture in a Mouse Model of Alzheimer’s Disease

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Jing Jiang ◽  
Gang Liu ◽  
Suhua Shi ◽  
Zhigang Li
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Frontal Lobe ◽  
Morris Water Maze ◽  
Water Maze ◽  
Morris Water Maze Test ◽  
Maze Test ◽  
Model Of Alzheimer’S Disease ◽  
Samp8 Mice

Objectives. To compare musical electroacupuncture and electroacupuncture in a mouse model of Alzheimer’s disease.Methods. In this study, 7.5-month-old male senescence-accelerated mouse prone 8 (SAMP8) mice were used as an Alzheimer’s disease animal model. In the normal control paradigm, 7.5-month-old male SAMR1 mice were used as the blank control group (N group). After 15 days of treatment, using Morris water maze test, micro-PET, and immunohistochemistry, the differences among the musical electroacupuncture (MEA), electroacupuncture (EA), Alzheimer’s disease (AD), and normal (N) groups were assessed.Results. The Morris water maze test, micro-PET, and immunohistochemistry revealed that MEA and EA therapies could improve spatial learning and memory ability, glucose metabolism level in the brain, and Aβamyloid content in the frontal lobe, compared with the AD group (P<0.05). Moreover, MEA therapy performed better than EA treatment in decreasing amyloid-beta levels in the frontal lobe of mice with AD.Conclusion. MEA therapy may be superior to EA in treating Alzheimer’s disease as demonstrated in SAMP8 mice.

scholarly journals EVALUATION OF ANTI-ALZHEIMER ACTIVITY OF ETHANOLIC AND METHANOLIC EXTRACTS OF POLYGONUM GLABRUM AGAINST ALUMINUM CHLORIDE-INDUCED ALZHEIMER’S IN EXPERIMENTAL RATS

2021 ◽  
pp. 118-125
Author(s):  
SUNEESHA Y ◽  
VINAY KUMAR T
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Aluminum Chloride ◽  
Methanolic Extract ◽  
Ethanolic Extract ◽  
Morris Water Maze Test ◽  
Methanolic Extracts ◽  
Maze Test ◽  
Behavioral Parameters ◽  
Acetylcholinesterase Enzyme

Objective: The current study aimed at the investigation of the effectiveness of ethanolic and methanolic extract of Polygonum glabrum in aluminum chloride-induced Alzheimer’s disease in experimental rats. Methods: The behavioral parameters evaluated by following methods such as Morris water maze test, radial arm maze test, and active avoidance test. Biochemical parameters were also estimated such as acetylcholine and acetylcholine esterase. Results: Polygonum glabrum extract was instituted to be neuroprotective against AlCl3-induced toxicity. Enhanced learning and memory were allied to the ingestion of extract in rats. Al overload, acetylcholinesterase enzyme hyperactivity is responsible for Alzheimer’s disease which is neutralized or reduced with treatment of extract, which might be due to the synergistic action of its active constituents. Ethanolic extract was shown slightly higher efficacy as compared to methanolic extract. Conclusion: Based on these current findings, it is suggested that lowering Aβ is an unproven strategy, and it may be time to refocus on other targets for the treatment of this disease, including pathological forms of tau.

scholarly journals Neuroprotective effects of verbascoside against Alzheimer’s disease via the relief of endoplasmic reticulum stress in Aβ-exposed U251 cells and APP/PS1 mice

2020 ◽  
Vol 17 (1) ◽  
Author(s):  
Chunyue Wang ◽  
Xueying Cai ◽  
Ruochen Wang ◽  
Siyu Zhai ◽  
Yongfeng Zhang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Amyloid Β ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Morris Water Maze Test ◽  
Proteomics Analysis ◽  
Neuroprotective Effects ◽  
U251 Cells

Abstract Background Endoplasmic reticulum (ER) stress is involved in the progression of Alzheimer’s disease (AD). Verbascoside (VB), an active phenylethanoid glycoside that was first isolated from Verbascum sinuatum (the wavyleaf mullein), possesses anti-inflammatory, antioxidative, and anti-apoptotic effects. The purpose of this study was to elucidate the beneficial effects of VB in amyloid β (Aβ)1–42-damaged human glioma (U251) cells and in APPswe/PSEN1dE9 transgenic (APP/PS1) mice. Methods U251 cells were co-incubated with 10 μM of Aβ1-42 and treated with VB. The protective effects of VB were investigated by using 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl tetrazolium bromide assay, flow cytometry, fluorescence staining, and transmission electron microscopy. APP/PS1 transgenic mice were treated for 6 weeks with VB. Learning and memory were evaluated using a Morris water maze test. Immunohistochemistry, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling, thioflavin-S staining, and proteomics analysis were performed to study the potential neuroprotective mechanism. Enzyme-linked immunosorbent assays and western blot were performed to analyze altered protein levels of brain lysates in APP/PS1 mice and/or Aβ1-42-damaged U251 cells. Results In Aβ1-42-damaged U251 cells, VB significantly improved cell viability, inhibited apoptosis, reduced calcium accumulation and the intracellular concentrations of reactive oxygen species, and improved the morphology of mitochondria and ER. In APP/PS1 mice, 6-week administration of VB significantly improved memory and cognition. VB inhibited apoptosis, reduced the deposition of Aβ, reduced the formation of neurofibrillary tangles formed by hyperphosphorylated tau protein, and downregulated the expression levels of 4-hydroxynonenal and mesencephalic astrocyte-derived neurotrophic factor in the brains of APP/PS1 mice. Proteomics analysis of mouse hippocampus suggested that the neuroprotective effect of VB may be related to the reduction of ER stress. This was indicated by the fact that VB inhibited the three branches of the unfolded protein response, thereby attenuating ER stress and preventing apoptosis. Conclusions The results confirmed that VB possesses significant neuroprotective effects, which are related to the reduction of ER stress. These findings support the status of VB as a potentially effective treatment for AD and warrant further research.

scholarly journals Coffee polyphenols prevent cognitive dysfunction and suppress amyloid β plaques in APP/PS2 transgenic mouse

2018 ◽  
Author(s):  
Keiko Ishida ◽  
Masaki Yamamoto ◽  
Koichi Misawa ◽  
Noriyasu Ota ◽  
Akira Shimotoyodome
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Transgenic Mouse ◽  
Cognitive Dysfunction ◽  
Amyloid Β ◽  
Morris Water Maze Test ◽  
Dependent Manner ◽  
Chlorogenic Acids ◽  
Caffeoylquinic Acid ◽  
Model Of Alzheimer’S Disease

AbstractEpidemiological studies have found that habitual coffee consumption may reduce the risk of Alzheimer’s disease. Coffee contains numerous phenolic compounds (coffee polyphenols) such as chlorogenic acids. However, evidence demonstrating the contribution of chlorogenic acids in preventing cognitive dysfunction induced by Alzheimer’s disease is limited. In this study, we investigated the effect of chlorogenic acids on prevention of cognitive dysfunction in APP/PS2 transgenic mouse model of Alzheimer’s disease. Five-week-old APP/PS2 mice were administered a diet supplemented with coffee polyphenols daily for 5 months. The memory and cognitive function of mice was determined using the novel object recognition test, the Morris water maze test, and the step-through passive avoidance test. We found that chronic treatment with coffee polyphenols prevented cognitive dysfunction and significantly reduced hippocampal Aβ deposition. We then determined the effect of 5-caffeoylquinic acid, one of the primary components of coffee polyphenols, on Aβ formation. 5-Caffeoylquinic acid did not inhibit Aβ fibrillation, but degraded Aβ fibrils in a dose-dependent manner. In conclusion, these results demonstrate that coffee polyphenols prevented cognitive deficits and alleviated Aβ plaque deposition via disaggregation of Aβ in APP/PS2 mouse.

scholarly journals Ameliorative effects of olibanum essential oil on learning and memory in Aβ1-42-induced Alzheimer’s disease mouse model

2020 ◽  
Vol 19 (8) ◽  
pp. 1643-1651
Author(s):  
Zhenzhen Zhang ◽  
Wenhua Chen ◽  
Jie Luan ◽  
Dagui Chen ◽  
Lina Liu ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Essential Oil ◽  
Learning And Memory ◽  
Hippocampal Neurons ◽  
Amyloid Β ◽  
Amyloid Plaques ◽  
Morris Water Maze Test ◽  
Amyloid Β Peptide ◽  
Brain Tissues

Purpose: To study the effect of olibanum essential oil (OEO) on learning and memory in Alzheimer’s disease (AD) mouse.Methods: Mice were administered the 42-amino acid form of amyloid β-peptide (Aβ1-42) to induce AD and then treated with OEO at 150, 300, and 600 mg/kg, p.o. for two weeks. Following treatment, the AD mice were assessed by step-down test (SDT), dark avoidance test (DAT), and Morris water maze test (MWM). Blood and brain tissues were collected for biochemical assessments. Gas chromatographymass spectroscopy was used to analyze the main constituents of OEO.Results: The main constituents of OEO were limonene, α-pinene, and 4-terpineol. Treatment with OEO prolonged t latency in SDT and DAT, but decreased error times. Escape latency decreased and crossing times were rose in the MWM following OEO treatment (p < 0.5). Treatment with OEO also enhanced the acetylcholine levels and decreased the acetylcholinesterase levels in serum and brain tissue (p < 0.5). Additionally, OEO reduced amyloid plaques in the hippocampus and protected hippocampal neurons from damage. Furthermore, OEO decreased c-fos expression in  hippocampus tissues from AD mice (p < 0.5).Conclusion: OEO has significant ameliorative effect AD-induced deterioration in learning and memory in AD mouse induced by Aβ1-42. The mechanisms of these effects are related to increased acetylcholine contents, reduction of amyloid plaques, protection of hippocampal neurons, and downregulation of c-fos in brain tissues. The results justify the need for further investigation of candidate drugs derived from OEO for the  management of AD. Keywords: Olibanum, Essential oil, Learning, Memory, AD

Cognitive enhancement of volatile oil from the stems of Schisandra chinensis Baill. in Alzheimer’s disease rats

2018 ◽  
Vol 96 (6) ◽  
pp. 550-555 ◽  
Author(s):  
Bingyou Yang ◽  
Bo Liu ◽  
Yan Liu ◽  
Hua Han ◽  
Haixue Kuang
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Deficits ◽  
Amyloid Β ◽  
Volatile Oil ◽  
Gas Chromatography Mass Spectrometry ◽  
Morris Water Maze Test ◽  
Schisandra Chinensis ◽  
Nerve Growth ◽  
Necrosis Factor

The volatile oil (VO), extracted from the stems of Schisandra chinensis Baill. (SCS), was separated and identified by gas chromatography – mass spectrometry. The study was devised to investigate the effects of VO on oxidative stress and cognitive deficits induced by amyloid-β (Aβ(1-42)). Alzheimer’s disease (AD) models were established by injecting Aβ(1-42) into the rat hippocampus and the effects of learning and memory were observed by a Morris water maze test, immunohistological alterations, and correlative indicators covering nerve growth (brain-derived neurotrophic factor, glial-cell-derived trophic factor, and nerve growth factor), interleukin 1β, tumor necrosis factor, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), malondialdehyde (MDA), glial fibrillary acidic protein (GFAP), and microglial CD11b in AD rats. And activities of SOD, MDA, and GSH-Px were ameliorated by VO. The neurotrophic factors GFAP and microglial CD11b were noticeably improved in histopathologic changes. These data suggested that VO from SCS had potential activities for the prevention and treatment of AD.

Gamma radiation preparation of chitosan nanoparticles for controlled delivery of memantine

2019 ◽  
Vol 34 (8) ◽  
pp. 1150-1162 ◽  
Author(s):  
Rasha R Radwan ◽  
Ashraf M Abdel Ghaffar ◽  
Hussein E Ali
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Gamma Radiation ◽  
Histopathological Examination ◽  
Chitosan Nanoparticles ◽  
Amyloid Β ◽  
Brain Targeting ◽  
Morris Water Maze Test ◽  
Infrared Analysis ◽  
Amyloid Β Peptide

The purpose of the current study is to prepare chitosan nanoparticles by gamma radiation as a new brain delivery system for memantine to improve its therapeutic efficiency. Fourier-transform infrared analysis of chitosan nanoparticles showed the characteristic peaks of chitosan and the reduction of particle size induced by irradiation at doses 10, 20 and 30 kGy. The solubility of chitosan nanoparticles was tested using different solvents and exhibited good solubility in both water and 1% acetic acid than other tested solvents at 80°C. Different formulations containing memantine -loaded chitosan nanoparticles were evaluated for brain targeting on aluminum-induced Alzheimer’s disease in rats. Memory deficit was evaluated using the Morris water maze test. The levels of amyloid-β peptide, tumour necrosis factor alpha, interleukin-1β and interleukin-6 in brain tissues as well as the serum level of brain-derived neurotrophic factor were assayed. Data demonstrated that memantine -loaded chitosan nanoparticles 1:1 transported memantine effectively into the brain compared to free memantine as evidenced by better behaviour performance and biochemical amelioration and confirmed by histopathological examination in Alzheimer’s disease rats. Interestingly, the therapeutic effect of memantine -loaded chitosan nanoparticles 1:1 was superior to memantine -loaded chitosan nanoparticles 1:2 and memantine -loaded chitosan nanoparticles 2:1. Based on these findings, it is reasonable to suggest that memantine -loaded chitosan nanoparticles 1:1 could be a promising approach for Alzheimer’s disease.

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