scholarly journals Effect of Vitamin D Supplementation on the Progression of Alzheimer’s Disease in Rats: A Mechanistic Approach

2021 ◽  
Author(s):  
Parmi Patel ◽  
Jigna Samir Shah
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Vitamin D ◽  
Vitamin D Supplementation ◽  
Cognitive Status ◽  
Tau Proteins ◽  
Biochemical Alterations ◽  
Vitamin D Levels ◽  
The Brain

Abstract Purpose: A multifaceted treatment approach can be effective for Alzheimer's disease (AD). However, currently, it involves only symptomatic treatment with cholinergic drugs. Beneficial effects of high vitamin D levels or its intake in the prevention and treatment of cognitive disorders have been reported. Thus, the present study examined the preventive effect of vitamin D supplementation on AD progression and evaluated its impact on the accumulation or degradation of Aβ plaques. Methods: A single intraperitoneal injection of scopolamine was used to induce AD in rats. Treatment of vitamin D was provided for 21 days after the injection. Various behavioral parameters like learning, spatial memory and exploratory behavior, biochemical alterations in the brain homogenate and histology of the hippocampus were investigated. Results: Our results indicated that scopolamine-induced rats depicted cognitive deficits with high Aβ levels and hyperphosphorylated tau proteins in the brain tissue, while vitamin D supplementation could significantly improve the cognitive status and lower these protein levels. These results were supported by the histopathological and immunohistochemical staining of the hippocampal brain region. Furthermore, mechanistic analysis depicted that vitamin D supplementation improved the Aβ protein clearance by increasing the neprilysin levels. It also reduced the accumulation of Aβ plaques by lowering neuroinflammation as well as oxidative stress. Conclusion: The present findings indicate that vitamin D supplementation can delay AD progression by an increase in Aβ plaques degradation or reducing inflammation and oxidative stress.

scholarly journals The non-genomic vitamin D pathway links β-amyloid to autophagic apoptosis in Alzheimer's disease

2021 ◽  
Author(s):  
Rai-Hua Lai ◽  
Yueh-Ying Hsu ◽  
Feng-Shiun Shie ◽  
Mei-Hsin Chen ◽  
Jyh-Lyh Juang
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Vitamin D ◽  
Cognitive Impairment ◽  
Vitamin D Deficiency ◽  
Epidemiological Studies ◽  
Vitamin D Supplementation ◽  
Adult Brain ◽  
Plasma Vitamin ◽  
Vitamin D Levels

Vitamin D is an important hormonal molecule, which exerts genomic and non-genomic actions in maintaining brain development and adult brain health. Many epidemiological studies have associated vitamin D deficiency with Alzheimer's disease (AD). Nevertheless, the underlying signaling pathway through which this occurs remains to be characterized. We were intrigued to find that although vitamin D levels are significantly low in AD patients, their hippocampal vitamin D receptor (VDR) levels are inversely increased in the cytosol of the brain cells, and colocalized with Aβ plaques, gliosis and autophagosomes, suggesting that a non-genomic form of VDR is implicated in AD. Mechanistically, Aβ induces the conversion of nuclear heterodimer of VDR/RXR heterodimer into a cytoplasmic VDR/p53 heterodimer. The cytosolic VDR/p53 complex mediates the Aβ induced autophagic apoptosis. Reduction of p53 activity in AD mice reverses the VDR/RXR formation and rescues AD brain pathologies and cognitive impairment. In line with the impaired genomic VDR pathway, the transgenic AD mice fed a vitamin D sufficient diet exhibit lower plasma vitamin D levels since early disease phases, raising the possibility that vitamin D deficiency may actually be an early manifestation of AD. Despite the deficiency of vitamin D in AD mice, vitamin D supplementation not only has no benefit but lead to exacerbated Aβ depositions and cognitive impairment. Together, these data indicate that the impaired genomic vitamin D pathway links Aβ to induce autophagic apoptosis, and suggest that VDR/p53 pathway could be targeted for the treatment of AD.

scholarly journals Low Vitamin D and Its Association with Cognitive Impairment and Dementia

2020 ◽  
Vol 2020 ◽  
pp. 1-10 ◽  
Author(s):  
Sadia Sultan ◽  
Uzma Taimuri ◽  
Shatha Abdulrzzaq Basnan ◽  
Waad Khalid Ai-Orabi ◽  
Afaf Awadallah ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Vitamin D ◽  
Cognitive Impairment ◽  
Behavioral Problems ◽  
Small Sample Size ◽  
Vitamin D Supplementation ◽  
Small Sample ◽  
Vitamin D Levels ◽  
Prevention And Treatment

Vitamin D is a neurosteroid hormone that regulates neurotransmitters and neurotrophins. It has anti-inflammatory, antioxidant, and neuroprotective properties. It increases neurotrophic factors such as nerve growth factor which further promotes brain health. Moreover, it is also helpful in the prevention of amyloid accumulation and promotes amyloid clearance. Emerging evidence suggests its role in the reduction of Alzheimer’s disease hallmarks such as amyloid-beta and phosphorylated tau. Many preclinical studies have supported the hypothesis that vitamin D leads to attentional, behavioral problems and cognitive impairment. Cross-sectional studies have consistently found that vitamin D levels are significantly low in individuals with Alzheimer’s disease and cognitive impairment compared to healthy adults. Longitudinal studies and meta-analysis have also exhibited an association of low vitamin D with cognitive impairment and Alzheimer’s disease. Despite such evidence, the causal association cannot be sufficiently answered. In contrast to observational studies, findings from interventional studies have produced mixed results on the role of vitamin D supplementation in the prevention and treatment of cognitive impairment and dementia. The biggest issue of the existing RCTs is their small sample size, lack of consensus over the dose, and age of initiation of vitamin D supplements to prevent cognitive impairment. Therefore, there is a need for large double-blind randomized control trials to assess the benefits of vitamin D supplementation in the prevention and treatment of cognitive impairment.

scholarly journals Potential of Sorghum Polyphenols to Prevent and Treat Alzheimer’s Disease: A Review Article

2021 ◽  
Vol 13 ◽  
Author(s):  
Nasim Rezaee ◽  
W.M.A.D. Binosha Fernando ◽  
Eugene Hone ◽  
Hamid R. Sohrabi ◽  
Stuart K. Johnson ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mitochondrial Dysfunction ◽  
Stress Reduction ◽  
Neuronal Damage ◽  
Tau Proteins ◽  
Farm Animals ◽  
Learning Impairments ◽  
The Brain

Alzheimer’s disease (AD) is characterized by the excessive deposition of extracellular amyloid-beta peptide (Aβ) and the build-up of intracellular neurofibrillary tangles containing hyperphosphorylated tau proteins. This leads to neuronal damage, cell death and consequently results in memory and learning impairments leading to dementia. Although the exact cause of AD is not yet clear, numerous studies indicate that oxidative stress, inflammation, and mitochondrial dysfunction significantly contribute to its onset and progression. There is no effective therapeutic approach to stop the progression of AD and its associated symptoms. Thus, early intervention, preferably, pre-clinically when the brain is not significantly affected, is a better option for effective treatment. Natural polyphenols (PP) target multiple AD-related pathways such as protecting the brain from Aβ and tau neurotoxicity, ameliorating oxidative damage and mitochondrial dysfunction. Among natural products, the cereal crop sorghum has some unique features. It is one of the major global grain crops but in the developed world, it is primarily used as feed for farm animals. A broad range of PP, including phenolic acids, flavonoids, and condensed tannins are present in sorghum grain including some classes such as proanthocyanidins that are rarely found in others plants. Pigmented varieties of sorghum have the highest polyphenolic content and antioxidant activity which potentially makes their consumption beneficial for human health through different pathways such as oxidative stress reduction and thus the prevention and treatment of neurodegenerative diseases. This review summarizes the potential of sorghum PP to beneficially affect the neuropathology of AD.

scholarly journals Failure of the Brain Glucagon-Like Peptide-1-Mediated Control of Intestinal Redox Homeostasis in a Rat Model of Sporadic Alzheimer’s Disease

Antioxidants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1118
Author(s):  
Jan Homolak ◽  
Ana Babic Perhoc ◽  
Ana Knezovic ◽  
Jelena Osmanovic Barilar ◽  
Melita Salkovic-Petrisic
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Rat Model ◽  
Redox Homeostasis ◽  
Brain State ◽  
Gastrointestinal Hormone ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
The Brain

The gastrointestinal system may be involved in the etiopathogenesis of the insulin-resistant brain state (IRBS) and Alzheimer’s disease (AD). Gastrointestinal hormone glucagon-like peptide-1 (GLP-1) is being explored as a potential therapy as activation of brain GLP-1 receptors (GLP-1R) exerts neuroprotection and controls peripheral metabolism. Intracerebroventricular administration of streptozotocin (STZ-icv) is used to model IRBS and GLP-1 dyshomeostasis seems to be involved in the development of neuropathological changes. The aim was to explore (i) gastrointestinal homeostasis in the STZ-icv model (ii) assess whether the brain GLP-1 is involved in the regulation of gastrointestinal redox homeostasis and (iii) analyze whether brain-gut GLP-1 axis is functional in the STZ-icv animals. Acute intracerebroventricular treatment with exendin-3(9-39)amide was used for pharmacological inhibition of brain GLP-1R in the control and STZ-icv rats, and oxidative stress was assessed in plasma, duodenum and ileum. Acute inhibition of brain GLP-1R increased plasma oxidative stress. TBARS were increased, and low molecular weight thiols (LMWT), protein sulfhydryls (SH), and superoxide dismutase (SOD) were decreased in the duodenum, but not in the ileum of the controls. In the STZ-icv, TBARS and CAT were increased, LMWT and SH were decreased at baseline, and no further increment of oxidative stress was observed upon central GLP-1R inhibition. The presented results indicate that (i) oxidative stress is increased in the duodenum of the STZ-icv rat model of AD, (ii) brain GLP-1R signaling is involved in systemic redox regulation, (iii) brain-gut GLP-1 axis regulates duodenal, but not ileal redox homeostasis, and iv) brain-gut GLP-1 axis is dysfunctional in the STZ-icv model.

Role of Vitamins in Neurodegenerative Diseases: A Review

2021 ◽  
Vol 20 ◽  
Author(s):  
Ravi Ranjan Kumar ◽  
Lovekesh Singh ◽  
Amandeep Thakur ◽  
Shamsher Singh ◽  
Bhupinder Kumar
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Vitamin D ◽  
Vitamin C ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Vitamin D Deficiency ◽  
Neurological Disorders ◽  
The Brain

Background: Vitamins are the micronutrients required for boosting the immune system and managing any future infection. Vitamins are involved in neurogenesis, a defense mechanism working in neurons, metabolic reactions, neuronal survival, and neuronal transmission. Their deficiency leads to abnormal functions in the brain like oxidative stress, mitochondrial dysfunction, accumulation of proteins (synuclein, Aβ plaques), neurodegeneration, and excitotoxicity. Methods: In this review, we have compiled various reports collected from PubMed, Scholar Google, Research gate, and Science direct. The findings were evaluated, compiled, and represented in this manuscript. Conclusion: The deficiency of vitamins in the body causes various neurological disorders like Alzheimer’s disease, Parkinson’s disease, Huntington's disease, and depression. We have discussed the role of vitamins in neurological disorders and the normal human body. Depression is linked to a deficiency of vitamin-C and vitamin B. In the case of Alzheimer’s disease, there is a lack of vitamin-B1, B12, and vitamin-A, which results in Aβ-plaques. Similarly, in Parkinson’s disease, vitamin-D deficiency leads to a decrease in the level of dopamine, and imbalance in vitamin D leads to accumulation of synuclein. In MS, Vitamin-C and Vitamin-D deficiency causes demyelination of neurons. In Huntington's disease, vitamin- C deficiency decreases the antioxidant level, enhances oxidative stress, and disrupts the glucose cycle. Vitamin B5 deficiency in Huntington's disease disrupts the synthesis of acetylcholine and hormones in the brain.

scholarly journals Metabolism: A Novel Shared Link between Diabetes Mellitus and Alzheimer’s Disease

2020 ◽  
Vol 2020 ◽  
pp. 1-12 ◽  
Author(s):  
Yanan Sun ◽  
Cao Ma ◽  
Hui Sun ◽  
Huan Wang ◽  
Wei Peng ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Metabolic Disease ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mitochondrial Dysfunction ◽  
Diabetic Patients ◽  
Increased Risk ◽  
Impaired Insulin ◽  
The Brain

As a chronic metabolic disease, diabetes mellitus (DM) is broadly characterized by elevated levels of blood glucose. Novel epidemiological studies demonstrate that some diabetic patients have an increased risk of developing dementia compared with healthy individuals. Alzheimer’s disease (AD) is the most frequent cause of dementia and leads to major progressive deficits in memory and cognitive function. Multiple studies have identified an increased risk for AD in some diabetic populations, but it is still unclear which diabetic patients will develop dementia and which biological characteristics can predict cognitive decline. Although few mechanistic metabolic studies have shown clear pathophysiological links between DM and AD, there are several plausible ways this may occur. Since AD has many characteristics in common with impaired insulin signaling pathways, AD can be regarded as a metabolic disease. We conclude from the published literature that the body’s diabetic status under certain circumstances such as metabolic abnormalities can increase the incidence of AD by affecting glucose transport to the brain and reducing glucose metabolism. Furthermore, due to its plentiful lipid content and high energy requirement, the brain’s metabolism places great demands on mitochondria. Thus, the brain may be more susceptible to oxidative damage than the rest of the body. Emerging evidence suggests that both oxidative stress and mitochondrial dysfunction are related to amyloid-β (Aβ) pathology. Protein changes in the unfolded protein response or endoplasmic reticulum stress can regulate Aβ production and are closely associated with tau protein pathology. Altogether, metabolic disorders including glucose/lipid metabolism, oxidative stress, mitochondrial dysfunction, and protein changes caused by DM are associated with an impaired insulin signal pathway. These metabolic factors could increase the prevalence of AD in diabetic patients via the promotion of Aβ pathology.

scholarly journals Cellular Senescence and Iron Dyshomeostasis in Alzheimer’s Disease

2019 ◽  
Vol 12 (2) ◽  
pp. 93 ◽  
Author(s):  
Shashank Masaldan ◽  
Abdel Ali Belaidi ◽  
Scott Ayton ◽  
Ashley I. Bush
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Hydroxyl Radicals ◽  
Iron Accumulation ◽  
Brain Iron ◽  
Dependent Cell ◽  
Cellular Dysfunction ◽  
The Impact ◽  
The Brain

Iron dyshomeostasis is a feature of Alzheimer’s disease (AD). The impact of iron on AD is attributed to its interactions with the central proteins of AD pathology (amyloid precursor protein and tau) and/or through the iron-mediated generation of prooxidant molecules (e.g., hydroxyl radicals). However, the source of iron accumulation in pathologically relevant regions of the brain and its contribution to AD remains unclear. One likely contributor to iron accumulation is the age-associated increase in tissue-resident senescent cells that drive inflammation and contribute to various pathologies associated with advanced age. Iron accumulation predisposes ageing tissue to oxidative stress that can lead to cellular dysfunction and to iron-dependent cell death modalities (e.g., ferroptosis). Further, elevated brain iron is associated with the progression of AD and cognitive decline. Elevated brain iron presents a feature of AD that may be modified pharmacologically to mitigate the effects of age/senescence-associated iron dyshomeostasis and improve disease outcome.

Oxidative Stress Targeting Amyloid Beta Accumulation and Clearance in Alzheimer’s Disease: Insight into Pathological Mechanisms and Therapeutic Strategies

2020 ◽  
Vol 9 (1) ◽  
pp. 22-42
Author(s):  
Sunpreet Kaur ◽  
Puneet Kumar ◽  
Shamsher Singh
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Beta ◽  
Neurodegenerative Disorder ◽  
Acetylcholinesterase Inhibitors ◽  
The Elderly ◽  
Biochemical Alterations ◽  
App Trafficking ◽  
Copper Aluminum

Background: Alzheimer’s disease is the most common neurodegenerative disorder affecting the elderly population and emerges as a leading challenge for the scientific research community. The wide pathological aspects of AD made it a multifactorial disorder and even after long time it’s difficult to treat due to unexplored etiological factors. Methods: The etiogenesis of AD includes mitochondrial failure, gut dysbiosis, biochemical alterations but deposition of amyloid-beta plaques and neurofibrillary tangles are implicated as major hallmarks of neurodegeneration in AD. The aggregates of these proteins disrupt neuronal signaling, enhance oxidative stress and reduce activity of various cellular enzymes which lead to neurodegeneration in the cerebral cortex, neocortex and hippocampus. The metals like copper, aluminum are involved in APP trafficking and promote amyloidbeta aggregation. Similarly, disturbed ubiquitin proteasomal system, autophagy and amyloid- beta clearance mechanisms exert toxic insult in the brain. Result and conclusion : The current review explored the role of oxidative stress in disruption of amyloid homeostasis which further leads to amyloid-beta plaque formation and subsequent neurodegeneration in AD. Presently, management of AD relies on the use of acetylcholinesterase inhibitors, antioxidants and metal chelators but they are not specific measures. Therefore, in this review, we have widely cited the various pathological mechanisms of AD as well as possible therapeutic targets.

Sign in / Sign up

Export Citation Format

Share Document