scholarly journals Neuroprotective Effects of Probiotic-Supplemented Diet on Cognitive Behavior of 3xTg-AD Mice

2022 ◽  
Vol 2022 ◽  
pp. 1-10
Author(s):  
Chenxi Tan ◽  
Yang Liu ◽  
Huiyi Zhang ◽  
Cihan Di ◽  
Dechao Xu ◽  
...  

Alzheimer’s disease (AD) is recognized as one of the most common types of senile dementia. AD patients first suffer memory loss for recent events (short-term memory impairment). As the disease progresses, they are deprived of self-awareness. This study aims to explore the effects of a probiotic-supplemented diet on the cognitive behaviors and pathological features of mouse models of Alzheimer’s disease (AD). Mice in the control group and the 3xTg-AD group were fed a regular diet and a probiotic-supplemented diet, respectively, for 20 weeks. Behavioral experiments like Morris’s water maze and Y maze were conducted. Then, feces of mice were collected for 16S sRNA gene sequencing for microorganisms. In the end, soluble and insoluble Aβ40 and Aβ42 in the hippocampus and cortex of mice in each group were quantitatively analyzed with a double-antibody Sandwich ELISA. The expression levels of tau protein and gliocyte in the hippocampus and cortex were detected using the Western Blot method. The result of the Morris water maze experiment indicated that, in the place navigation test, the mice in the 3xTg-AD group experienced a significant decline in the learning ability and a longer escape latency and in the space exploration test, the swimming time of mice in the 3xTg-AD group in the target quadrant decreased and after being treated with the probiotic diet, mice in the 3xTg-AD group had improved learning and memory ability. The result of Y maze showed that the probiotic diet can improve the spontaneous alternation accuracy of mice in the 3xTg-AD group. The result of 16s rRNA gene sequencing showed that, compared with mice in the WT group, those in the 3xTg-AD group experienced a change in the intestinal flora. The Western Blot result displayed a decreased expression level of tau (pS202) ( P < 0.05 ) and decreased expression levels of Iba-1 and GFAP ( P < 0.05 ). The result of the ELISA experiment showed decreased levels of soluble and insoluble Aβ40 and Aβ42 in 3xTg-AD mice ( P < 0.05 ). In conclusion, a probiotic diet can prevent and treat AD by improving the intestinal flora of 3xTg-AD.

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Jun Sung Park ◽  
Sang Tae Kim ◽  
Sang Yun Kim ◽  
Min Gi Jo ◽  
Myeong Jun Choi ◽  
...  

Abstract Alzheimer’s disease (AD) is a progressive neurodegenerative disease and chronic illness with long preclinical phases and a long clinical duration. Until recently, a lack of potential therapeutic agents against AD was the primary focus of research, which resulted in less effort directed towards developing useful diagnostic approaches. In this study, we developed a WO2002/088706 kit that is composed of fluorescent nanoparticles for the early detection of AD. We provided a fluorescent nanoparticle for detecting markers and a kit for the early diagnosis of AD. The kit consists of a probe molecule comprising an oligonucleotide capable of detecting one or more AD-specific microRNAs (miRNAs) and biomarkers related to AD. Through screening, we selected miR-106b, miR-146b, miR-181a, miR-200a, miR-34a, miR-124b, miR-153, miR-155, Aβ1-42 monomer (mAβ), Aβ1–42 oligomer (oAβ), UCHL1, NLRP3, Tau, STAT3, SORL1, Clusterin, APOE3, APOE4, Nogo-A, IL-13, and Visfatin to serve as AD- and inflammation-related markers. For detection of kit-binding properties, we checked the expression levels of amyloid beta (Aβ), tau protein, and inflammatory mediators in APP/PS/ApoE knockdown (KD) mice and a control group using co-localisation analysis conducted with a confocal microscope. Using a similar approach, we checked the expression levels of miRNAs in HT22 cells. Finally, we used the plasma from AD patients to confirm that our fluorescent nanoparticles and the WO2002/088706 kit will provide a possible early diagnosis to serve as an AD detector that can be further improved for future studies on targeting AD.


2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Shaodong Deng ◽  
Hongmei Lu ◽  
Honggang Chi ◽  
Ying Wang ◽  
Xiao Li ◽  
...  

Morinda officinalis F.C. How. (Rubiaceae) is a herbal medicine. It has been recorded that its oligosaccharides have neuroprotective properties. In order to understand the oligosaccharides extracted from Morinda officinalis (OMO), a systematic study was conducted to provide evidence that supports its use in neuroprotective therapies for Alzheimer’s disease (AD). AD rat models were prepared with D-galactose and Aβ25–35. The following groups were used in the present experiment: normal control group, sham-operated group, model group, Aricept group, OMO low-dose group, OMO medium-dose group, and OMO high-dose group. The effects on behavioral tests, antioxidant levels, energy metabolism, neurotransmitter levels, and AD-related proteins were detected with corresponding methodologies. AD rats administered with different doses of OMO all exhibited a significant (P<0.05) decrease in latency and an increase (P<0.05) in the ratio of swimming distance to total distance in a dose-dependent manner in the Morris water maze. There was a significant (P<0.05) increase in antioxidant enzyme activities (SOD, GSH-Px, and CAT), neurotransmitter levels (acetylcholine, γ-GABA, and NE and DA), energy metabolism (Na+/K+-ATPase), and relative synaptophysin (SYP) expression levels in AD rats administered with OMO. Furthermore, there was a significant (P<0.05) decrease in MDA levels and relative expression levels of APP, tau, and caspase-3 in AD rats with OMO. The present research suggests that OMO protects against D-galactose and Aβ25–35-induced neurodegeneration, which may provide a novel strategy for improving AD in clinic.


2020 ◽  
Vol 8 (A) ◽  
pp. 476-480
Author(s):  
Faradila Faradila ◽  
Yuliarni Syafrita ◽  
Nur Indrawaty Lipoeto

BACKGROUND: At present, there is no pharmacological therapy that can cure Alzheimer’s disease. Treatment is only limited to preventing progression and controlling risk factors that worsen Alzheimer’s. Medium-chain triglycerides (MCT) are nutritional therapies that are being studied to prevent the progression of Alzheimer’s disease. AIM: This study aims to see the effect of giving MCT to the value of percentage alternation Y-maze test and serum Aβ-42 levels as a marker of Alzheimer’s disease. MATERIALS AND METHODS: This study is an experimental study using postp-test control group design. Samples from this study were 30 Sprague Dawley rats which were divided into positive control groups, negative controls, and three treatment groups. Positive control group and treatment were induced by Alzheimer’s by ovariectomy and d-galactose. After induction, MCT were given to the treatment group for 6 weeks. After treatment, the levels of Aβ-42 serum were examined by ELISA and cognitive function was examined by Y-maze. After that, the data were analyzed by ANOVA. p < 0.05 was said to be statistically significant. RESULTS: The results showed that this study was found a moderate relationship with a positive pattern. This means that the higher the percentage alternation value, the higher the level of Aβ-42 in serum which indicates that the higher the percentage alternation value, the higher the clearance of Aβ-42. CONCLUSION: This study concluded that the group of rats given MCT has a serum Aβ-42 level higher than the group of rats that were not given MCT.


Gerontology ◽  
2022 ◽  
pp. 1-13
Author(s):  
Xuezhi Zhang ◽  
Wenwen Yu ◽  
Xuelei Cao ◽  
Yongbin Wang ◽  
Chao Zhu ◽  
...  

<b><i>Aim:</i></b> The aim of this study is to identify potential serum biomarkers of Alzheimer’s disease (AD) for early diagnosis and to evaluate these markers on a large cohort. <b><i>Methods:</i></b> We performed two-dimensional difference gel electrophoresis to compare the serum of AD patients and normal controls. Western blot or enzyme-linked immunosorbent assay (ELISA) was used to identify the expression levels of proteins. <b><i>Results:</i></b> In this study, a total of 13 differentially expressed proteins were identified. Among them, 2 proteins (inter-alpha-trypsin inhibitor heavy chain H4 [ITI-H4], Apolipoprotein A-IV) were validated by Western blot and 4 proteins (Cofilin 2, Tetranectin, Zinc-alpha-2-glycoprotein [AZGP1], Alpha-1-microglobulin/bikunin precursor [AMBP]) were validated by ELISA, respectively. Western blot results showed that the full size of the ITI-H4 protein was increased, while a fragment of ITI-H4 was decreased in AD patients. In contrast, 1 fragment of Apo A-IV was mainly found in control group and rare to be detected in AD patients. On the other hand, ELISA results showed that Cofilin 2, Tetranectin, AZGP1, and AMBP were significantly increased in AD patients, and Cofilin 2 is strongly correlated with the Mini-Mental State Examination scores of the AD patients. Serum Cofilin 2 was unchanged in Parkinson disease patients as compared to the control group, indicating a specific correlation of serum Cofilin 2 with AD. Moreover, Cofilin 2 was increased in both the serum and brain tissue in the APP/PS1 transgenic mice. <b><i>Conclusion:</i></b> Our study identified several potential serum biomarkers of AD, including: ITI-H4, ApoA-IV, Cofilin 2, Tetranectin, AZGP1, and AMBP. Cofilin 2 was upregulated in different AD animal models and might play important roles in AD pathology.


2016 ◽  
Vol 34 (3) ◽  
pp. 215-222 ◽  
Author(s):  
Xinsheng Lai ◽  
Jie Ren ◽  
Yangjia Lu ◽  
Shaoyang Cui ◽  
Junqi Chen ◽  
...  

Objective To explore the effects of acupuncture at HT7 on different cerebral regions in a rat model of Alzheimer's disease (AD) with the application of 18F-2-fluoro-deoxy-D-glucose positron emission tomography (FDG-PET). Methods Sixty Wistar rats were included after undergoing a Y-maze electric sensitivity test. Ten rats were used as a healthy control group. The remaining 50 rats were injected stereotaxically with ibotenic acid into the right nucleus basalis magnocellularis and injected intraperitoneally with D-galactose. AD was successfully modelled in 36 rats, which were randomly divided into three groups (n=12 each): the AD group, which remained untreated; the AD+HT7 group, which received 20 sessions of acupuncture at HT7 over 1 month; and the AD+Sham group, which received acupuncture at a distant non-acupuncture point. Total reaction time (TRT) was measured by Y-maze and 18F-FDG-PET scans were conducted on day 1 and 30. PET images were processed with Statistical Parametric Mapping 8.0. Results Pre-treatment, TRT was greater in all AD groups versus controls (mean±SD 24.10±2.48 vs 41.34±5.00 s). Post-treatment, TRT was shortened in AD+HT7 versus AD+Sham and AD groups (p<0.0001, two-way analysis of variance). Glucose metabolic activity in the hippocampus, thalamus, hypothalamus, frontal lobe, and temporal lobe was decreased in AD rats compared with healthy controls and relatively elevated after HT7 acupuncture. Compared with sham acupuncture, HT7 needling had a greater positive influence on brain glucose metabolism. Conclusions Needling at HT7 can improve memory ability and cerebral glucose metabolic activity of the hippocampus, thalamus, hypothalamus, and frontal/temporal lobes in an AD rat model.


2021 ◽  
Vol 12 ◽  
Author(s):  
Feng Wang ◽  
Xi-Xi Wei ◽  
Lian-Sheng Chang ◽  
Lei Dong ◽  
Yong-Ling Wang ◽  
...  

Background: Brain-derived nerve growth factor (BDNF) is a promising effective target for the treatment of Alzheimer’s disease (AD). BDNF, which has a high molecular weight, has difficulty in crossing the blood–brain barrier (BBB). The study aimed to prepare microbubbles loading brain-derived nerve growth factor (BDNF) retrovirus (MpLXSN-BDNF), to verify the characteristics of the microbubbles, and to study the therapeutic effect of the microbubbles combined with ultrasound on the opening of the blood–brain barrier in an AD rat model.Methods: 32 adult male SD rats were randomly divided into four groups: control group, ultrasound + pLXSN-EGFP microbubble group (U + MpLXSN-BDNF), ultrasound + pLXSN-BDNF microbubble group, and ultrasound + microbubble + pLXSN-BDNF virus group (U + MpLXSN-BDNF), with eight rats in each group. At the same time, the left hippocampus of rats was irradiated with low-frequency focused ultrasound guided by MRI to open the blood–brain barrier (BBB). The effects of BDNF overexpression on AD rats were evaluated behaviorally before and 1 month after the treatment. The number of acetylcholinesterase (ChAT)-positive cells and the content of acetylcholine (ACh) in brain tissues were determined by immunohistochemistry and high-performance liquid chromatography (HPLC), respectively. IF staining of synaptic spines and Western blot of synaptophysin presented herein detected synaptic density recovery.Results: Signal intensity enhancement at the BBB disruption sites could be observed on the MR images. The behavioral evaluation showed that the times of crossing the original platform in the U + MpLXSN-BDNF group increased significantly after treatment. Immunohistochemistry and HPLC revealed that the number of ChAT-positive neurons and the contents of ACh in the brain were significantly decreased in the treated groups compared with the controls. IF staining of synaptic spines and Western blot data of synaptophysin showed that the U + MpLXSN-BDNF group can recover the synaptic loss better by BDNF supplementation than the other treatment groups.Conclusion: Ultrasound combined with viral microbubbles carrying BDNF can increase the transfection efficiency of brain neurons, promote the high expression of exogenous gene BDNF, and play a therapeutic role in the AD model rats.


2021 ◽  
Vol 12 ◽  
Author(s):  
Xingxing Zhao ◽  
Hongmei Yao ◽  
Xinyi Li

Alzheimer’s disease (AD) is a neurodegenerative disease with unelucidated molecular pathogenesis. Herein, we aimed to identify potential hub genes governing the pathogenesis of AD. The AD datasets of GSE118553 and GSE131617 were collected from the NCBI GEO database. The weighted gene coexpression network analysis (WGCNA), differential gene expression analysis, and functional enrichment analysis were performed to reveal the hub genes and verify their role in AD. Hub genes were validated by machine learning algorithms. We identified modules and their corresponding hub genes from the temporal cortex (TC), frontal cortex (FC), entorhinal cortex (EC), and cerebellum (CE). We obtained 33, 42, 42, and 41 hub genes in modules associated with AD in TC, FC, EC, and CE tissues, respectively. Significant differences were recorded in the expression levels of hub genes between AD and the control group in the TC and EC tissues (P &lt; 0.05). The differences in the expressions of FCGRT, SLC1A3, PTN, PTPRZ1, and PON2 in the FC and CE tissues among the AD and control groups were significant (P &lt; 0.05). The expression levels of PLXNB1, GRAMD3, and GJA1 were statistically significant between the Braak NFT stages of AD. Overall, our study uncovered genes that may be involved in AD pathogenesis and revealed their potential for the development of AD biomarkers and appropriate AD therapeutics targets.


2020 ◽  
Author(s):  
Qianqian Chen ◽  
Jinpeng Wu ◽  
Huijuan Yin ◽  
Xiaoxi Dong ◽  
Xiafei Shi ◽  
...  

Abstract Background: Emerging evidence suggests that the gut microbiota plays an important role in the pathological progression of Alzheimer’s disease (AD). Photobiomodulation (PBM) therapy is believed to have a positive regulatory effect on the imbalance of certain body functions, including inflammation, immunity, wound healing, nerve repair, and pain. Previous studies have found that the intestinal flora of patients with AD is in an unbalanced state. Therefore, we have proposed the use of gut flora-targeted PBM (gf-targeted PBM) as a method to improve AD in an Aß-induced AD mouse model. Methods: PBM was performed on the abdomen of the mice at the wavelengths of 630 nm, 730 nm, and 850 nm at 100 J/cm2 for 8 weeks. Morris water maze test, immunofluorescence and proteomic of hippocampus, and intestinal flora detection of fecal were used to evaluate the treatment effects of gf-targeted PBM on AD rats.Results: PBM at all three wavelengths (especially 630 nm and 730 nm) significantly improved learning retention as measured by the Morris water maze. In addition, we found reduced amyloidosis and tau phosphorylation in the hippocampus by immunofluorescence in AD mice. By using a quantitative proteomic analysis of the hippocampus, we found that gf-targeted PBM significantly altered the expression levels of 509 proteins (the same differentially expressed proteins in all three wavelengths of PBM), which involved the pathways of hormone synthesis, phagocytosis, and metabolism. The 16s rRNA gene sequencing of fecal contents showed that PBM significantly altered the diversity and abundance of intestinal flora. Specifically, PBM treatment reversed the typical increase of Helicobacter and uncultured Bacteroidales and the decrease of Rikenella seen in AD mice. Conclusions: Our data indicate that gf-targeted PBM regulates the diversity of intestinal flora, which may improve damage caused by AD. Gf-targeted PBM has the potential to be a noninvasive microflora regulation method for AD patients.


2020 ◽  
Vol 23 (4) ◽  
pp. 524-539
Author(s):  
Fatemeh Heidari Soureshjani ◽  
◽  
Majid Kheirollahi ◽  
Parichehreh Yaghmaei ◽  
Fattah Sotoodehnejadnematalahi ◽  
...  

Background and Aim: Alzheimerchr('39')s Disease (AD) is a neurodegenerative brain disease that gradually destroys memory and cognitive skills. The disease is caused by the formation of beta-amyloid plaques, oxidative stress, dysfunctions in the cholinergic system, neuronal killing inflammation, and ultimately brain atrophy. Donepezil and hyoscyamoside have inhibitory effects on these pathogens; therefore, their impact on the learning process of Alzheimer’s rats in the Morris Water Maze was investigated. Methods & Materials: In the present experimental study, 60 male rats of Wistar breed with approximately 7 weeks age within the control group (rats that received normal water and food), the PBS group (underwent surgery), PBS group (received solvent Aβ), the first Alzheimer›s group (animals that received beta-amyloid by Alzheimer’s surgery, second Alzheimer’s group (after Alzheimer’s surgery, they received 1 cc of normal saline daily, and treatment groups that treated the rats with beta-amyloid after Alzheimer. In the hyoscyamoside group, they received 10 mg/kg daily of hyoscyamoside for 28 days. The donepezil group received it 4 mg/kg daily for 28 days by gavage. The Morris Water Maze test was used to evaluate learning and memory. Data were analyzed by ANOVA statistical analysis and Post Hoc test. Ethical Considerations: The Ethics Committee in Biomedical Research, Islamic Azad University, Science and Research Branch approved the research (Code: IR.IAU.SRB.REC 1397.057) Results: Beta-amyloid injection caused extensive damage to memory. The treatment groups with hyoscyamoside and donepezil spent less time and distance with a significant level (P<0.001) than the group of Alzheimer’s patients to find the hidden platform. In the reminder phase, where the previously hidden platform was located, they spent more time, with a significant level (P<0.001) in the local quarter. Conclusion: Treatment of rats with hyoscyamoside and donepezil improved spatial memory in Alzheimer’s rats. They appear to play a significant role in the prevention and treatment of Alzheimer’s disease.


2020 ◽  
Vol 48 (08) ◽  
pp. 1803-1819
Author(s):  
Yong Ho Ku ◽  
Jae Hui Kang ◽  
Hyun Lee

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.


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