scholarly journals Protective role of Dihydromyricetin in Alzheimer’s disease rat model associated with activating AMPK/SIRT1 signaling pathway

2019 ◽  
Vol 39 (1) ◽  
Author(s):  
Ping Sun ◽  
Jun-Bo Yin ◽  
Li-Hua Liu ◽  
Jian Guo ◽  
Sheng-Hai Wang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Signaling Pathway ◽  
Inflammatory Cytokines ◽  
Rat Model ◽  
Inflammatory Responses ◽  
Protective Role ◽  
Spatial Learning And Memory ◽  
Related Proteins

Abstract The aim of the present study was to understand the possible role of the Dihydromyricetin (DHM) in Alzheimer’s disease (AD) rat model through regulation of the AMPK/SIRT1 signaling pathway. Rats were divided into Sham group, AD group, AD + DHM (100 mg/kg) group and AD + DHM (200 mg/kg) group. The spatial learning and memory abilities of rats were assessed by Morris Water Maze. Then, the inflammatory cytokines expressions were determined by radioimmunoassay while expressions of AMPK/SIRT1 pathway-related proteins by Western blot; and the apoptosis of hippocampal cells was detected by TdT-mediated dUTP nick end labeling assay. AD rats had an extended escape latency with decreases in the number of platform crossings, the target quadrant residence time, as well as swimming speed, and the inflammatory cytokines in serum and hippocampus were significantly elevated but AMPK/SIRT1 pathway-related proteins were reduced. Meanwhile, the apoptosis of hippocampal cells was significantly up-regulated with decreased Bcl-2 and increased Bax, as compared with Sham rats (all P<0.05). After AD rats treated with 100 or 200 mg/kg of DHM, the above effects were significantly reversed, resulting in a completely opposite tendency, and especially with 200 mg/kg DHM treatment, the improvement of AD rats was more obvious. DHM exerts protective role in AD via up-regulation of AMPK/SIRT1 pathway to inhibit inflammatory responses and hippocampal cell apoptosis and ameliorate cognitive function.

scholarly journals Crosstalk between Gut and Brain in Alzheimer’s Disease: The Role of Gut Microbiota Modulation Strategies

Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 690
Author(s):  
Umair Shabbir ◽  
Muhammad Sajid Arshad ◽  
Aysha Sameen ◽  
Deog-Hwan Oh
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Gut Microbiota ◽  
Dietary Habits ◽  
Inflammatory Responses ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Gut Dysbiosis ◽  
Dynamic Population

The gut microbiota (GM) represents a diverse and dynamic population of microorganisms and about 100 trillion symbiotic microbial cells that dwell in the gastrointestinal tract. Studies suggest that the GM can influence the health of the host, and several factors can modify the GM composition, such as diet, drug intake, lifestyle, and geographical locations. Gut dysbiosis can affect brain immune homeostasis through the microbiota–gut–brain axis and can play a key role in the pathogenesis of neurodegenerative diseases, including dementia and Alzheimer’s disease (AD). The relationship between gut dysbiosis and AD is still elusive, but emerging evidence suggests that it can enhance the secretion of lipopolysaccharides and amyloids that may disturb intestinal permeability and the blood–brain barrier. In addition, it can promote the hallmarks of AD, such as oxidative stress, neuroinflammation, amyloid-beta formation, insulin resistance, and ultimately the causation of neural death. Poor dietary habits and aging, along with inflammatory responses due to dysbiosis, may contribute to the pathogenesis of AD. Thus, GM modulation through diet, probiotics, or fecal microbiota transplantation could represent potential therapeutics in AD. In this review, we discuss the role of GM dysbiosis in AD and potential therapeutic strategies to modulate GM in AD.

scholarly journals Astrocytes and neuroinflammation in Alzheimer's disease

2014 ◽  
Vol 42 (5) ◽  
pp. 1321-1325 ◽  
Author(s):  
Emma C. Phillips ◽  
Cara L. Croft ◽  
Ksenia Kurbatskaya ◽  
Michael J. O’Neill ◽  
Michael L. Hutton ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Inflammatory Responses ◽  
Amyloid Β ◽  
Synaptic Dysfunction ◽  
Amyloid Β Peptide ◽  
Substantial Evidence ◽  
Models Of Disease ◽  
Opposing Effects

Increased production of amyloid β-peptide (Aβ) and altered processing of tau in Alzheimer's disease (AD) are associated with synaptic dysfunction, neuronal death and cognitive and behavioural deficits. Neuroinflammation is also a prominent feature of AD brain and considerable evidence indicates that inflammatory events play a significant role in modulating the progression of AD. The role of microglia in AD inflammation has long been acknowledged. Substantial evidence now demonstrates that astrocyte-mediated inflammatory responses also influence pathology development, synapse health and neurodegeneration in AD. Several anti-inflammatory therapies targeting astrocytes show significant benefit in models of disease, particularly with respect to tau-associated neurodegeneration. However, the effectiveness of these approaches is complex, since modulating inflammatory pathways often has opposing effects on the development of tau and amyloid pathology, and is dependent on the precise phenotype and activities of astrocytes in different cellular environments. An increased understanding of interactions between astrocytes and neurons under different conditions is required for the development of safe and effective astrocyte-based therapies for AD and related neurodegenerative diseases.

scholarly journals Effects of Chronic Administration of Pioglitazone on Learning and Memory in Rat Model of Streptozotocin-induced Alzheimer’s Disease

2020 ◽  
Vol 24 (4) ◽  
pp. 294-307
Author(s):  
Ehsan Aali ◽  
◽  
Mohammad Hossein Esmaeili ◽  
Sead Shima Mahmodi ◽  
Poriea Solimani ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Learning And Memory ◽  
Spatial Learning ◽  
Rat Model ◽  
Escape Latency ◽  
Chronic Administration ◽  
Spatial Learning And Memory ◽  
Swimming Time

Background: Alzheimer’s Disease (AD) is a chronic neurodegenerative disease characterized by abnormal protein accumulation, synaptic dysfunction, and cognitive impairment. Peroxisome Proliferator-Activated Receptor-γ (PPARγ) play a crucial role in regulating insulin sensitivity and may serve as potential therapeutic targets for AD. Pioglitazone (PIOG), as a PPARγ agonist, reduces β-amyloid and tau proteins, and inhibits neuroinflammation. Objective: This study aims to evaluate the effects of PIOG chronic administration on learning and memory in rat model of Streptozotocin (STZ)-induced AD Methods: Forty-two male Wistar rats were divided into two groups: A. Normal rats divided into three subgroups of Control, Dimethyl Sulfoxide (DMSO), and PIOG; and B. AD rats divided into four subgroups of Vehicle, STZ, STZ+DMSO and STZ+PIOG. The last two AD subgroups received 0.2 mL DMSO and PIOG (10 mg/kg per day) for 21 days. For induction of AD, STZ (3 mg/kg, 10 μl per injection site) were administered into lateral ventricles. All rates were trained under the Morris water maze task. Findings: PIOG impaired the spatial learning and memory in normal rats. Intracerebroventricular injection of STZ significantly increased escape latency and swimming time to find the hidden platform compared to the control group (P<0.05). The amnesic effect of STZ was prevented by PIOG administration such that the escape latency and swimming time to find the hidden platform in the STZ+PIOG group were significantly lower than in the STZ+DMSO group (P<0.05). Conversely, the percentage of time spent and distance swimming in the target quadrant in the probe test in the STZ+ PIOG group rats were significantly higher than those in the STZ + DMSO group. Conclusion: PIOG administration impaired spatial learning and memory in normal rats, but improved learning and memory in rats with STZ-induced AD. It can be useful for treatment of cognitive impairment in AD patients.

Novel Therapeutic Mechanism of Action of Metformin and Its Nanoformulation in Alzheimer's Disease and Role of AKT/ERK/GSK Pathway.

2021 ◽  
Author(s):  
Harish Kumar ◽  
Amitava Chakrabarti ◽  
Phulen Sarma ◽  
Manish Modi ◽  
Dibyajyoti Banerjee ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Disease Control ◽  
Rat Model ◽  
Memory Impairment ◽  
Protective Efficacy ◽  
Control Group ◽  
Hyperphosphorylated Tau ◽  
Days Of Therapy

Abstract Background: Insulin resistance in brain plays a critical role in the pathogenesis of Alzheimer's disease (AD). Metformin is a blood brain barrier crossing anti-diabetic insulin-sensitizer drug. Current study has evaluated the therapeutic and mechanistic role of conventional as well as solid lipid nanoformulation (SLN) of metformin in intracerebro ventricular (ICV) Aβ (1-42) rat-model of AD. Methods: SLN-metformin was prepared by the micro-emulsification method and further evaluated by zetasizer and scanning electron-microscopy. In the animal experimental phase, AD was induced by bilateral ICV injection of Aβ using stereotaxic technique, whereas control group (sham) received ICV-NS. 14 days post-model induction, ICV- Aβ treated rats were further divided into 5 groups: disease control (no treatment), Metformin dose of (50mg/kg, 100mg/kg and 150 mg/kg), SLN of metformin 50mg/kg and memantine 1.8mg/kg (positive-control). Animals were tested for cognitive performance (in EPM, MWM) after 21 days of therapy, and then sacrificed. Brain homogenate was evaluated using ELISA for (Aβ (1-42), hyperphosphorylated tau, pAKTser473, GSK-3β, p-ERK,) and HPLC (metformin level). Brain histopathology was used to evaluate neuronal injury score (H&E) and Bcl2 and BAX (IHC). Results: The average size of SLN-metformin was <200 nm and was of spherical in shape with 94.08% entrapment efficiency. Compared to sham, the disease-control group showed significantly higher (p≤0.05) memory impairment (in MWM and EPM), higher hyperphosphorylated tau, Aβ (1-42), and Bax and lower Bcl-2 expression. Metformin was detectable in brain. Treatment with metformin and its SLN form significantly decreased the memory impairment as well as decreased the expression of hyperphosphorylated tau, Aβ(1-42), Bax expression and increased expression of Bcl-2 in brain. AKT-ERK-GSK3β-Hyperphosphorylated tau pathway can be implicated in the protective efficacy of metformin. Conclusion: Both metformin and SLN metformin is found to be effective as therapeutic agent in ICV-AB rat model of AD. AKT-ERK-GSK3β-Hyperphosphorylated tau pathway is found to be involved in the protective efficacy of metformin.

The modulatory role of phloretin in Aβ25–35 induced sporadic Alzheimer’s disease in rat model

2018 ◽  
Vol 392 (3) ◽  
pp. 327-339 ◽  
Author(s):  
Priya J. Ghumatkar ◽  
Sachin P. Patil ◽  
Vaibhavi Peshattiwar ◽  
Tushara Vijaykumar ◽  
Vikas Dighe ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Rat Model ◽  
Sporadic Alzheimer’S Disease

scholarly journals Genetic Variants of Lipoprotein Lipase and Regulatory Factors Associated with Alzheimer’s Disease Risk

2020 ◽  
Vol 21 (21) ◽  
pp. 8338
Author(s):  
Kimberley D. Bruce ◽  
Maoping Tang ◽  
Philip Reigan ◽  
Robert H. Eckel
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Lipoprotein Lipase ◽  
Genetic Variants ◽  
Disease Risk ◽  
Lipoprotein Metabolism ◽  
Protective Role ◽  
Direct Role ◽  
The Brain

Lipoprotein lipase (LPL) is a key enzyme in lipid and lipoprotein metabolism. The canonical role of LPL involves the hydrolysis of triglyceride-rich lipoproteins for the provision of FFAs to metabolic tissues. However, LPL may also contribute to lipoprotein uptake by acting as a molecular bridge between lipoproteins and cell surface receptors. Recent studies have shown that LPL is abundantly expressed in the brain and predominantly expressed in the macrophages and microglia of the human and murine brain. Moreover, recent findings suggest that LPL plays a direct role in microglial function, metabolism, and phagocytosis of extracellular factors such as amyloid- beta (Aβ). Although the precise function of LPL in the brain remains to be determined, several studies have implicated LPL variants in Alzheimer’s disease (AD) risk. For example, while mutations shown to have a deleterious effect on LPL function and expression (e.g., N291S, HindIII, and PvuII) have been associated with increased AD risk, a mutation associated with increased bridging function (S447X) may be protective against AD. Recent studies have also shown that genetic variants in endogenous LPL activators (ApoC-II) and inhibitors (ApoC-III) can increase and decrease AD risk, respectively, consistent with the notion that LPL may play a protective role in AD pathogenesis. Here, we review recent advances in our understanding of LPL structure and function, which largely point to a protective role of functional LPL in AD neuropathogenesis.

scholarly journals Alzheimer's disease and periodontitis - an elusive link

2014 ◽  
Vol 60 (2) ◽  
pp. 173-180 ◽  
Author(s):  
Abhijit N. Gurav
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Inflammatory Cytokines ◽  
Critical Role ◽  
Anaerobic Bacteria ◽  
Systemic Infection ◽  
Low Grade ◽  
Inflammatory Status ◽  
Pro Inflammatory Cytokines

Alzheimer's disease is the preeminent cause and commonest form of dementia. It is clinically characterized by a progressive descent in the cognitive function, which commences with deterioration in memory. The exact etiology and pathophysiologic mechanism of Alzheimer's disease is still not fully understood. However it is hypothesized that, neuroinflammation plays a critical role in the pathogenesis of Alzheimer's disease. Alzheimer's disease is marked by salient inflammatory features, characterized by microglial activation and escalation in the levels of pro-inflammatory cytokines in the affected regions. Studies have suggested a probable role of systemic infection conducing to inflammatory status of the central nervous system. Periodontitis is common oral infection affiliated with gram negative, anaerobic bacteria, capable of orchestrating localized and systemic infections in the subject. Periodontitis is known to elicit a "low grade systemic inflammation" by release of pro-inflammatory cytokines into systemic circulation. This review elucidates the possible role of periodontitis in exacerbating Alzheimer's disease. Periodontitis may bear the potential to affect the onset and progression of Alzheimer's disease. Periodontitis shares the two important features of Alzheimer's disease namely oxidative damage and inflammation, which are exhibited in the brain pathology of Alzheimer's disease. Periodontitis can be treated and hence it is a modifiable risk factor for Alzheimer's disease.

P.5.029 Putative protective role of glutamateantibodies in Alzheimer's disease

2005 ◽  
Vol 15 ◽  
pp. S217
Author(s):  
T.V. Davidova ◽  
V.G. Fomina ◽  
N.I. Voskresenskaya ◽  
L.A. Vetrile ◽  
N.A. Trekova ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Protective Role
Sign in / Sign up

Export Citation Format

Share Document