APPLICATION OF PIXE IN MEDICAL STUDY: ENVIRONMENTAL MINERALS AND NEURODEGENERATIVE DISORDERS

1999 ◽  
Vol 09 (03n04) ◽  
pp. 245-257 ◽  
Author(s):  
S. Yoshida
Keyword(s):  
Hippocampal Neurons ◽  
Green Fluorescence ◽  
Kii Peninsula ◽  
Al Content ◽  
Medical Study ◽  
Environmental Status ◽  
Alzheimer's Neurofibrillary Tangles ◽  
High Al Content ◽  
Lateral Sclerosis

Comparative study on amyotrophic lateral sclerosis (ALS) and parkinsonism-dementia (PDC) in the Kii Peninsula of Japan and Guam was conducted to evaluate the participatory role of environmental minerals in the pathogenesis of the above neurodegenerative diseases, using particle-induced x-ray emission (PIXE) spectrometry and morphometric-statistical analysis. A significantly high content of Al in the hippocampus and spinal cord of Kii and Guamanian ALS/PD cases was found with a positive correlation for Fe and Cu , and a negative correlation for Zn . The numbers of hippocampal neurons in Guamanian PDC, Alzheimer's disease, and Parkinson's disease were significantly decreased with a high Al content. Al content significantly and positively correlated with the number of Alzheimer's neurofibrillary tangles (NFTs) in the hippocampus of ALS cases and controls in both foci, especially in Guamanian cases. The slope of best linear regression of Guamanian cases was markedly steeper than that of Japanese cases ( p < 0.001). Morin staining for Al showed green fluorescence on the nucleolus, cytoplasm, and NFT in the hippocampus of Kii ALS cases. These findings suggest that Guamanian and Kii people have a predisposition to develop ALS/PDC precipitated by their geological/geochemical environmental status, i.e., a prolonged low intake of Ca and Mg together with excess exposure to Al and other environmental minerals.

scholarly journals Lake sedimentary biogenic silica from diatoms constitutes a significant global sink for aluminium

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Dong Liu ◽  
Peng Yuan ◽  
Qian Tian ◽  
Hongchang Liu ◽  
Liangliang Deng ◽  
...  
Keyword(s):  
Biogenic Silica ◽  
Biogeochemical Cycle ◽  
Biochemical Processes ◽  
Al Content ◽  
High Al Content ◽  
Global Oceans

Abstract Diatoms play an important role in marine biogeochemical cycle of aluminum (Al), as dissolved Al is taken up by diatoms to build their siliceous frustules and is involved in the sedimentation of diatomaceous biogenic silica (BSi). The Al incorporation in BSi facilitates decreasing the dissolution of marine BSi and thus substantially influences the biochemical processes driven by diatoms, such as CO2 sequestration. However, the role of lake BSi in the terrestrial biochemical Al cycle has not been explored, though lakes represent the second-largest sink for BSi. By identifying the previously unexplored high Al/Si atomic ratios (up to 0.052) in lake BSi, here we show lake BSi is a large terrestrial Al pool due to its high Al content, and lake sedimentary BSi constitutes a significant global sink for Al, which is on the same magnitude as the Al sink in global oceans.

ENVIRONMENTAL MINERALS IN KII AMYOTROPHIC LATERAL SCLEROSIS IN JAPAN: A PIXE ANALYSIS FEATURING ALUMINUM

1996 ◽  
Vol 06 (03n04) ◽  
pp. 543-554 ◽  
Author(s):  
SOHEI YOSHIDA ◽  
IKURO WAKAYAMA ◽  
TAMEKO KIHIRA ◽  
KAZUHISA SASAJIMA ◽  
KOJI YOSHIDA
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
High Ratio ◽  
Lumbar Spinal Cord ◽  
Geochemical Environment ◽  
Pixe Analysis ◽  
Al Content ◽  
Sporadic Als ◽  
Alzheimer's Neurofibrillary Tangles ◽  
Lumbar Spinal ◽  
Lateral Sclerosis

To evaluate a participatory role of environmental minerals in the pathogenesis of amyotrophic lateral sclerosis (ALS) in the Kii Peninsula of Japan, one of the three high-incidence foci, elemental and neuropathological investigations of lumbar spinal cord and hippocampal tissues were conducted, using particle-induced x-ray emission (PIXE) spectrometry and histomorphometric analysis. The PIXE analysis revealed extremely high contents of Al in both tissues of Kii ALS cases as compared with sporadic ALS and control cases. Morphometric analysis in the hippocampus showed abundant Alzheimer’s neurofibrillary tangles (NFTs) in the Kii ALS cases as compared with the other cases. Al content significantly correlated with the density of NFTs in all ALS cases ( r =0.765, p < 0.0001). Interestingly, both Al content and density of NFTs in the hippocampus of all ALS cases significantly and negatively correlated with Ca and Mg contents in the birthplace area’s rivers. The extremely low Ca and Mg content in the focus rivers was confirmed along with the high ratio of Al 2 O 3/ CaO in the soil. Thus, Kii ALS patients may reflect the geochemical environment of their birthplace, i.e., long term Ca and Mg deficiencies and excess Al accumulation along with widespread NFT formation in the brain.

The Role of Autophagy: What can be Learned from the Genetic Forms of Amyotrophic Lateral Sclerosis

2010 ◽  
Vol 9 (3) ◽  
pp. 268-278 ◽  
Author(s):  
Livia Pasquali ◽  
Riccardo Ruffoli ◽  
Federica Fulceri ◽  
Sara Pietracupa ◽  
Gabriele Siciliano ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Lateral Sclerosis

scholarly journals Cortical and Striatal Electroencephalograms and Apomorphine Effects in the FUS Mouse Model of Amyotrophic Lateral Sclerosis

2021 ◽  
pp. 1-15
Author(s):  
Vasily Vorobyov ◽  
Alexander Deev ◽  
Frank Sengpiel ◽  
Vladimir Nebogatikov ◽  
Aleksey A. Ustyugov
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Motor Neurons ◽  
Cortical Neurons ◽  
Primary Motor Cortex ◽  
Beta Activity ◽  
Systemic Injection ◽  
Eeg Spectra ◽  
Electroencephalogram Eeg ◽  
Lateral Sclerosis

Background: Amyotrophic lateral sclerosis (ALS) is characterized by degeneration of motor neurons resulting in muscle atrophy. In contrast to the lower motor neurons, the role of upper (cortical) neurons in ALS is yet unclear. Maturation of locomotor networks is supported by dopaminergic (DA) projections from substantia nigra to the spinal cord and striatum. Objective: To examine the contribution of DA mediation in the striatum-cortex networks in ALS progression. Methods: We studied electroencephalogram (EEG) from striatal putamen (Pt) and primary motor cortex (M1) in ΔFUS(1–359)-transgenic (Tg) mice, a model of ALS. EEG from M1 and Pt were recorded in freely moving young (2-month-old) and older (5-month-old) Tg and non-transgenic (nTg) mice. EEG spectra were analyzed for 30 min before and for 60 min after systemic injection of a DA mimetic, apomorphine (APO), and saline. Results: In young Tg versus nTg mice, baseline EEG spectra in M1 were comparable, whereas in Pt, beta activity in Tg mice was enhanced. In older Tg versus nTg mice, beta dominated in EEG from both M1 and Pt, whereas theta and delta 2 activities were reduced. In younger Tg versus nTg mice, APO increased theta and decreased beta 2 predominantly in M1. In older mice, APO effects in these frequency bands were inversed and accompanied by enhanced delta 2 and attenuated alpha in Tg versus nTg mice. Conclusion: We suggest that revealed EEG modifications in ΔFUS(1–359)-transgenic mice are associated with early alterations in the striatum-cortex interrelations and DA transmission followed by adaptive intracerebral transformations.

scholarly journals Tethering-induced destabilization and ATP-binding for tandem RRM domains of ALS-causing TDP-43 and hnRNPA1

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mei Dang ◽  
Yifan Li ◽  
Jianxing Song
Keyword(s):  
Conformational Dynamics ◽  
Md Simulations ◽  
Atp Binding ◽  
Rna Recognition Motif ◽  
Rna Recognition ◽  
Nucleic Acid Binding ◽  
General Role ◽  
Nmr Characterization ◽  
Lateral Sclerosis

AbstractTDP-43 and hnRNPA1 contain tandemly-tethered RNA-recognition-motif (RRM) domains, which not only functionally bind an array of nucleic acids, but also participate in aggregation/fibrillation, a pathological hallmark of various human diseases including amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), alzheimer's disease (AD) and Multisystem proteinopathy (MSP). Here, by DSF, NMR and MD simulations we systematically characterized stability, ATP-binding and conformational dynamics of TDP-43 and hnRNPA1 RRM domains in both tethered and isolated forms. The results reveal three key findings: (1) upon tethering TDP-43 RRM domains become dramatically coupled and destabilized with Tm reduced to only 49 °C. (2) ATP specifically binds TDP-43 and hnRNPA1 RRM domains, in which ATP occupies the similar pockets within the conserved nucleic-acid-binding surfaces, with the affinity slightly higher to the tethered than isolated forms. (3) MD simulations indicate that the tethered RRM domains of TDP-43 and hnRNPA1 have higher conformational dynamics than the isolated forms. Two RRM domains become coupled as shown by NMR characterization and analysis of inter-domain correlation motions. The study explains the long-standing puzzle that the tethered TDP-43 RRM1–RRM2 is particularly prone to aggregation/fibrillation, and underscores the general role of ATP in inhibiting aggregation/fibrillation of RRM-containing proteins. The results also rationalize the observation that the risk of aggregation-causing diseases increases with aging.

scholarly journals A modular tool to query and inducibly disrupt biomolecular condensates

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Carmen N. Hernández-Candia ◽  
Sarah Pearce ◽  
Chandra L. Tucker
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Cellular Function ◽  
Biological Role ◽  
Cellular Biology ◽  
Condensate Formation ◽  
Health And Disease ◽  
Lateral Sclerosis

AbstractDynamic membraneless compartments formed by protein condensates have multifunctional roles in cellular biology. Tools that inducibly trigger condensate formation have been useful for exploring their cellular function, however, there are few tools that provide inducible control over condensate disruption. To address this need we developed DisCo (Disassembly of Condensates), which relies on the use of chemical dimerizers to inducibly recruit a ligand to the condensate-forming protein, triggering condensate dissociation. We demonstrate use of DisCo to disrupt condensates of FUS, associated with amyotrophic lateral sclerosis, and to prevent formation of polyglutamine-containing huntingtin condensates, associated with Huntington’s disease. In addition, we combined DisCo with a tool to induce condensates with light, CRY2olig, achieving bidirectional control of condensate formation and disassembly using orthogonal inputs of light and rapamycin. Our results demonstrate a method to manipulate condensate states that will have broad utility, enabling better understanding of the biological role of condensates in health and disease.

scholarly journals Downregulation of miR-383 reduces depression-like behavior through targeting Wnt family member 2 (Wnt2) in rats

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shanshan Liu ◽  
Qing Liu ◽  
Yanjie Ju ◽  
Lei Liu
Keyword(s):  
Inflammatory Response ◽  
Family Member ◽  
Chronic Stress ◽  
Hippocampal Neurons ◽  
Luciferase Reporter ◽  
Mild Stress ◽  
Neural Injury ◽  
Expression Levels ◽  
Qrt Pcr

AbstractThis study aimed to evaluate the role of miR-383 in the regulation of Wnt-2 signaling in the rat model of chronic stress. The male SD rats with depressive-like behaviors were stimulated with chronic unpredictable mild stress (CUMS) including ice-water swimming for 5 min, food deprivation for 24 h, water deprivation for 24 h, stimulating tail for 1 min, turning night into day, shaking for 15 min (once/s), and wrap restraint (5 min/time) every day for 21 days. The expression levels of miRNAs were detected by qRT-PCR, and the expression levels of Wnt2, depression-impacted proteins (GFAP, BDNF, CREB), brain neurotransmitters (5-HT, NE, DA) and apoptosis-related proteins (Bax and Bcl-2) were evaluated by qRT-PCR and western blot. Bioinformatic analysis and luciferase reporter assay were performed to determine the relationship between miR-383 and Wnt2. Ethological analysis was evaluated by sugar preference test, refuge island test and open field tests. Rescue experiments including knockdown of miR-383, overexpression and silencing of Wnt2 were performed to determine the role of miR-383. High expression levels of miR-383 were observed in the hippocampus of rats submitted to CUMS model. Downregulation of miR-383 significantly inhibited the apoptosis and inflammatory response of hippocampal neurons, and increased the expression levels of GFAP, BDNF and CREB which were impacted in depression, as well as neurotransmitters, then attenuated neural injury in rats induced by CUMS. Furthermore, Wnt family member 2 (Wnt2) was identified as a target of miR-383, and silencing of Wnt2 obviously attenuated the protective effect of miR-383 inhibitor on the apoptosis and inflammatory response in hippocampal neurons, as well as neural injury in CUMS-induced rats. Downregulation of miR-383 ameliorated the behavioral and neurochemical changes induced by chronic stress in rats by directly targeting Wnt2, indicating that the miR-383/Wnt2 axis might be a potential therapeutic target for MDD.

scholarly journals Optineurin pathology in the spinal cord of amyotrophic lateral sclerosis/parkinsonism-dementia complex patients in Kii Peninsula, Japan

2018 ◽  
Vol 28 (3) ◽  
pp. 422-426 ◽  
Author(s):  
Satoru Morimoto ◽  
Hiroyuki Hatsuta ◽  
Rie Motoyama ◽  
Yasumasa Kokubo ◽  
Hiroyuki Ishiura ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Amyotrophic Lateral Sclerosis ◽  
Kii Peninsula ◽  
Complex Patients ◽  
Lateral Sclerosis
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