ALUMINUM NEUROTOXICITY IN THE RAT BRAIN

1992 ◽  
Vol 02 (04) ◽  
pp. 493-504 ◽  
Author(s):  
S. YUMOTO ◽  
H. OHASHI ◽  
H. NAGAI ◽  
S. KAKIMI ◽  
Y. OGAWA ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Rat Brain ◽  
Morphological Changes ◽  
Brain Cell ◽  
Nerve Cells ◽  
Cell Nuclei ◽  
Pixe Analysis ◽  
Aluminum Neurotoxicity ◽  
The Brain

To investigate the etiology of Alzheimer’s disease, we administered aluminum to healthy rats and examined the aluminum uptake in the brain and isolated brain cell nuclei by particle-induced X-ray emission (PIXE) analysis. Ten days after the last injection, Al was detected in the rat brain and in isolated brain cell nuclei by PIXE analysis. Al was also demonstrated in the brain after 15 months of oral aluminum administration. Moreover, Al was detected in the brain and isolated brain cell nuclei from the patients with Alzheimer’s disease. Silver impregnation studies revealed that spines attached to the dendritic processes of cortical nerve cells decreased remarkably after aluminum administration. Electron microscopy revealed characteristic inclusion bodies in the hippocampal nerve cells 75 days after the injection. These morphological changes in the rat brain after the aluminum administration were similar to those reportedly observed in the brain of Alzheimer’s disease patients. Our results indicate that Alzheimer’s disease is caused by irreversible accumulation of aluminum in the brain, as well as in the nuclei of brain cells.

MICROPROBE PIXE ANALYSIS AND EDX ANALYSIS ON THE BRAIN OF PATIENTS WITH ALZHEIMER’S DISEASE

1996 ◽  
Vol 06 (01n02) ◽  
pp. 193-204 ◽  
Author(s):  
S. YUMOTO ◽  
Y. HORINO ◽  
Y MOKUNO ◽  
K. FUJII ◽  
S. KAKIMI ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Senile Dementia ◽  
Heavy Ion ◽  
Cell Nuclei ◽  
Pixe Analysis ◽  
X Ray ◽  
Edx Analysis ◽  
The Brain ◽  
Higher Sensitivity

To investigate the cause of Alzheimer’s disease (senile dementia of Alzheimer’s disease type), we examined aluminium (Al) in the brain (hippocampus) of patients with Alzheimer’s disease using heavy ion (5 MeV Si 3+) microprobe particle-induced X-ray emission (PIXE) analysis. Heavy ion microprobes (3 MeV Si 2+) have several times higher sensitivity for Al detection than 2 MeV proton microprobes. We also examined Al in the brain of these patients by energy dispersive X-ray spectroscopy (EDX). (1) Al was detected in the cell nuclei isolated from the brain of patients with Alzheimer’s disease using 5 MeV Si 3+ microprobe PIXE analysis, and EDX analysis. (2) EDX analysis demonstrated high levels of Al in the nucleolus of nerve cells in frozen sections prepared from the brain of these patients. Our results support the theory that Alzheimer’s disease is caused by accumulation of Al in the nuclei of brain cells.

Morphological Changes of Microvessels in the Brain with Alzheimer's Disease

1988 ◽  
Vol 42 (4) ◽  
pp. 819-824 ◽  
Author(s):  
Taihei Miyakawa ◽  
Yasuo Uehara ◽  
Junzo Desaki ◽  
Takemi Kimura ◽  
Ryoko Kuramoto
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Morphological Changes ◽  
The Brain

ANALYSIS OF THE BRAIN TISSUES FROM A PATIENT WITH ALZHEIMER'S DISEASE AND EFFECTS OF CHELATING TREATMENT

1999 ◽  
Vol 09 (03n04) ◽  
pp. 297-303 ◽  
Author(s):  
A. M. EKTESSABI ◽  
S. FUJISAWA ◽  
K. TAKADA ◽  
K. YOSHIDA ◽  
H. MURAYAMA ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Sample Preparation ◽  
Dominant Role ◽  
Essential Elements ◽  
Pixe Analysis ◽  
Causative Factors ◽  
Measurement Results ◽  
The Brain ◽  
Excessive Accumulation

Alzheimer's, Parkinson's disease and ALS are among major neurodegenerative diseases. The cause of neurodegeneration is unknown, but there are indications that excessive accumulation of essential elements, and sometimes, incorporation of toxic foreign elements in neurons aggravate neurodegeneration. During the past decade, many researchers investigated the causative factors in degenerative diseases to specify genetic or environmental factor. PIXE analysis has been used for these studies because of the sample preparation is easy and detection limit is very low. However, the concentration of matrix elements and foreign elements are extremely low and difficult to detect and to quantify. In this study, specimens from patients with Alzheimer's disease with no chemical treatment, and those with chelating were analyzed. In all analyzed specimens, Na , Al , Si , P , S , Cl , Ca , Ti , V , Cr , Fe and Cu were detected. Each specimen in this study consisted of cerebral cortex and substantia alba. From these experiments we can observe a clear tendency that the accumulation of the metal elements are different depending on the constituent tissues, and the method of sample preparation has a dominant role in the measurement results.

scholarly journals Recovery of Dementia Syndrome following Treatment of Brain Inflammation

2020 ◽  
Vol 10 (1) ◽  
pp. 1-12 ◽  
Author(s):  
Jong-hoon Lee ◽  
Su-hee Choi ◽  
Chul Joong Lee ◽  
Sang-suk Oh
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Brain Cell ◽  
Brain Inflammation ◽  
Japanese Study ◽  
Long Period ◽  
Dementia Syndrome ◽  
Leprosy Patients ◽  
The Brain

Aim/Background: This research aims to prevent progression from mild cognitive impairment (MCI) to Alzheimer’s disease. A Japanese study of leprosy patients revealed that the incidence of dementia in leprosy patients was lower than that in patients taking dapsone who had never been treated. But a similar study the following year refuted the finding of less dementia in leprosy patients taking dapsone. According to conflicting reports, Mycobacterium leprae was a factor in reducing the incidence of Alzheimer’s disease. Thus, we formed a hypothesis that if dapsone is administered to patients without leprosy but with MCI and the prophylactic effect of dementia syndrome is observed over a long period of time, we can determine whether dapsone can prevent the progression of MCI to dementia syndrome. If dementia does not occur after treating inflammation in brain cells while dementia develops after a certain long-term period (usually within 2–3 years), brain cell inflammation can be demonstrated as the cause of dementia. Methods: This is a prospective cohort research. We report on an elderly patient diagnosed with MCI from February 2008 to January 2019. The patient took dapsone 100 mg once a day from 2010 to 2015 for the treatment of MCI. Since 2016, the production of dapsone has ceased in Korea. In June 2018, the patient was diagnosed with Alzheimer’s disease. The patient took Aricept for the treatment of Alzheimer’s disease but complained of serious side effects. And dapsone was re-administered to the patient from November 2018. Results: The patient recovered to MCI and improved her daily life owing to the treatment with dapsone. The drug controls the inflammatory response in the brain, irrespective of whether proteins are deposited in neurons. Conclusions:This finding means that dementia syndrome is an inflammatory disease. This research suggests that diagnostic criteria for Alzheimer’s disease should be based on the presence or absence of inflammation in neurons. Because inflammation in neurons can occur in middle age due to various causes, we can treat inflammation in neurons and prevent and treat dementia syndrome, including Alzheimer’s disease.

scholarly journals Rapid HPLC-ESI-MS/MS Analysis of Neurotransmitters in the Brain Tissue of Alzheimer’s Disease Rats before and after Oral Administration of Xanthoceras sorbifolia Bunge

Molecules ◽  
2018 ◽  
Vol 23 (12) ◽  
pp. 3111 ◽  
Author(s):  
Zheng Sun ◽  
Qing Li ◽  
Kaishun Bi
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Oral Administration ◽  
Rat Brain ◽  
Multiple Reaction Monitoring ◽  
New Drugs ◽  
Precipitation Method ◽  
Acetyl Choline ◽  
Pre Treatment ◽  
The Brain

In order to explore the potential therapeutic effect of Xanthoceras sorbifolia Bunge. against Alzheimer’s disease, an HPLC-MS/MS method has been developed and validated for simultaneous determination in rat brain of eight neurotransmitters, including dopamine, norepinephrine, 5-hydroxy-tryptamine, acetylcholine, l-tryptophan, γ-aminobutyric acid, glutamic acid and aspartic acid with a simple protein precipitation method for sample pre-treatment. The brain samples were separated on a polar functional group embedded column, then detected on a 4000 QTrap HPLC-MS/MS system equipped with a turbo ion spray source in positive ion and multiple reaction monitoring mode. The method was fully validated to be precise and accurate within the linearity range of the assay, and successfully applied to compare the neurotransmitters in the rat brain from four groups of normal, Alzheimer’s disease, and the oral administration group of X. sorbifolia extract and huperzine. The results indicated that brain levels of dopamine, norepinephrine and acetyl choline all decreased in the AD rats, while l-tryptophan showed an opposite trend. After administration of the Xanthoceras sorbifolia extract and huperzine, the level of acetyl choline and tryptophan returned to normal. Combination of the metabolic analysis, the results indicated that acetyl choline and l-tryptophan could be employed as therapy biomarkers for AD, and the results shown that the crude extract of the husks from Xanthoceras sorbifolia might ameliorate the impairment of learning and memory in the Alzheimer’s disease animal model with similar function of AchEI as huperzine. The established method would provide an innovative and effective way for the discovery of novel drug against Alzheimer’s disease, and stimulate a theoretical basis for the design and development of new drugs.

Sigma-2 Receptor as a Potential Drug Target

2020 ◽  
Vol 27 ◽  
Author(s):  
Ai-Fang Cheng ◽  
Wen-Hui Ma ◽  
Xiao-Yang Xie ◽  
Yun-Sheng Huang
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Nerve Cells ◽  
Anticancer Activities ◽  
Proliferating Cells ◽  
Aβ Oligomers ◽  
Tumor Cell Apoptosis ◽  
Therapeutic Development ◽  
Tumor Drugs ◽  
The Brain

: Sigma-2 receptor plays key roles in promoting tumor cell apoptosis, enhancing efficacy of anti-tumor drugs, blocking signal transduction controlled by Aβ oligomers, regulating Ca2+ homeostasis and protecting nerve cells. Studies indicated that sigma-2 receptor may be closely coupled with ROS, LDL, mTOR, RAS, PLC/PKC, lysosomal autophagy and mitochondrial super oxidative stress. In addition, the high expression of this receptor in proliferating cells and nerve cells indicates that sigma-2 receptor is an ideal molecular target for imaging and therapeutic development for cancer, Alzheimer's disease, schizophrenia and traumatic brain injury. Various sigma-2 agonists have shown promising anticancer activities, while sigma-2 antagonists have displayed neuroprotection and inhibition of Aβ oligomers in the brain of Alzheimer's disease patients. Thus, both sigma-2 agonists and antagonists are potentially useful therapeutics for management of cancer and neurodegenerative disorders.

scholarly journals DIVERGENT EFFECT OF CENTRAL INCRETIN RECEPTORS INHIBITION IN A RAT MODEL OF SPORADIC ALZHEIMER'S DISEASE

2021 ◽  
Author(s):  
Jelena Osmanovic Barilar ◽  
Ana Knezovic ◽  
Jan Homolak ◽  
Ana Babic Perhoc ◽  
Melita Salkovic-Petrisic
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Rat Model ◽  
Cell Metabolism ◽  
Hormone Secretion ◽  
Gastric Inhibitory Polypeptide ◽  
Brain Cell ◽  
Sporadic Alzheimer’S Disease ◽  
The Brain

The incretin system is an emerging new field that might provide valuable contributions to the research of both pathophysiology and therapeutic strategies in the treatment of diabetes, obesity, and neurodegenerative disorders. This study aimed to explore the role of central glucagon-like peptide-1 (GLP-1) and gastric inhibitory polypeptide (GIP) on cell metabolism and energy in the brain as well as on the levels of these incretins, insulin and glucose, by inhibiting the central incretins' receptors following intracerebroventricular administration of the respective antagonists in healthy rats and a streptozotocin-induced rat model of sporadic Alzheimer's disease (sAD). Chemical ablation of the central GIP receptor (GIPR) or GLP-1 receptor (GLP-1R) in healthy and diseased animals indicated a region-dependent role of incretins in the brain cell energy and metabolism and central incretin-dependent modulation of peripheral hormone secretion, markedly after GIPR inhibition, as well as a dysregulation of the GLP-1 system in experimental sAD.

Ubiquinone, dolichol, and cholesterol metabolism in aging and Alzheimer's disease

1992 ◽  
Vol 70 (6) ◽  
pp. 422-428 ◽  
Author(s):  
Conny Edlund ◽  
Magnus Söderberg ◽  
Krister Kristensson ◽  
Gustav Dallner
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mevalonate Pathway ◽  
Cholesterol Metabolism ◽  
Morphological Changes ◽  
Phospholipid Composition ◽  
Significant Elevation ◽  
P Concentration ◽  
Parallel Increase ◽  
The Brain

The lipid compositions of various regions of the human brain were investigated during aging and in Alzheimer's disease. The phospholipid amounts and compositions remained unchanged during aging. There were, however, considerable differences both in phospholipid composition and amount when the various regions were compared. The level of dolichol increased severalfold in all regions up to the age of 70, but there was no further elevation thereafter. The ubiquinone level decreased significantly in all parts of the brain upon aging. In Alzheimer's disease, the dolichol level was decreased in all regions, and particularly, in those affected by the disease. In contrast, the dolichyl-P concentration increased in those regions that exhibited morphological changes. There was no modification in cholesterol distribution, but a significant elevation in ubiquinone content was observed in most regions. The only phospholipid whose level was elevated was phosphatidylinositol, and only in those parts of the brain that were affected. The content of polyunsaturated fatty acids in phosphatidylethanolamine was greatly decreased in connection with the disease, with a parallel increase in the saturated portion. The results indicate that Alzheimer's disease results in specific and significant changes in the levels of lipid products of the mevalonate pathway in the brain.Key words: ubiquinone, dolichol, cholesterol, aging, Alzheimer's disease.

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