Organic Metal Species as Risk Factor for Neurological Diseases

Author(s):  
Sören Meyer ◽  
Till Weber ◽  
Robert Haferkorn-Starke ◽  
Tanja Schwerdtle ◽  
Julia Bornhorst
2019 ◽  
Vol 12 (603) ◽  
pp. eaay0300 ◽  
Author(s):  
Lucie I. Pisella ◽  
Jean-Luc Gaiarsa ◽  
Diabé Diabira ◽  
Jinwei Zhang ◽  
Ilgam Khalilov ◽  
...  

KCC2 is a vital neuronal K+/Cl− cotransporter that is implicated in the etiology of numerous neurological diseases. In normal cells, KCC2 undergoes developmental dephosphorylation at Thr906 and Thr1007. We engineered mice with heterozygous phosphomimetic mutations T906E and T1007E (KCC2E/+) to prevent the normal developmental dephosphorylation of these sites. Immature (postnatal day 15) but not juvenile (postnatal day 30) KCC2E/+ mice exhibited altered GABAergic inhibition, an increased glutamate/GABA synaptic ratio, and greater susceptibility to seizure. KCC2E/+ mice also had abnormal ultrasonic vocalizations at postnatal days 10 to 12 and impaired social behavior at postnatal day 60. Postnatal bumetanide treatment restored network activity by postnatal day 15 but failed to restore social behavior by postnatal day 60. Our data indicate that posttranslational KCC2 regulation controls the GABAergic developmental sequence in vivo, indicating that deregulation of KCC2 could be a risk factor for the emergence of neurological pathology.


2008 ◽  
Vol 182 (1-3) ◽  
pp. 31-44 ◽  
Author(s):  
Jolanta Galazka-Friedman

2021 ◽  
Vol 20 (2) ◽  
pp. 224-227
Author(s):  
Elena Caires Silveira ◽  

COVID-19 is a multisystemic disease with a wild severity range, being some chronic diseases risk factors for unfavorable evolution. It has been suggested are chronic neurological diseases are associated to higher mortality in COVID-19 patients; such association however, has not been described enough. In this context, this study seeks to evaluate whether the presence of previous chronic neurological disease is a factor associated with higher mortality in hospitalized severe cases of COVID-19. For this, the association between those variables was investigated in 87,871 patients through univariate (risk ratio and χ2 test) and multivariate (Poisson regression) analysis. It was found that the mortality rate for patients presenting chronic neurological disease was 23% higher (),this being an independent and statistically significant association (RR = 1.23, 95% CI = 1.2-1.3; p-value < 0.001). Therefore, more studies are needed to better characterize this association.


Biomolecules ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. 1119 ◽  
Author(s):  
Amany Tawfik ◽  
Yara A. Samra ◽  
Nehal M. Elsherbiny ◽  
Mohamed Al-Shabrawey

Elevated plasma homocysteine (Hcy) level, known as hyperhomocysteinemia (HHcy) has been linked to different systemic and neurological diseases, well-known as a risk factor for systemic atherosclerosis and cardiovascular disease (CVD) and has been identified as a risk factor for several ocular disorders, such as diabetic retinopathy (DR) and age-related macular degeneration (AMD). Different mechanisms have been proposed to explain HHcy-induced visual dysfunction, including oxidative stress, upregulation of inflammatory mediators, retinal ganglion cell apoptosis, and extracellular matrix remodeling. Our previous studies using in vivo and in vitro models of HHcy have demonstrated that Hcy impairs the function of both inner and outer blood retinal barrier (BRB). Dysfunction of BRB is a hallmark of vision loss in DR and AMD. Our findings highlighted oxidative stress, ER stress, inflammation, and epigenetic modifications as possible mechanisms of HHcy-induced BRB dysfunction. In addition, we recently reported HHcy-induced brain inflammation as a mechanism of blood–brain barrier (BBB) dysfunction and pathogenesis of Alzheimer’s disease (AD). Moreover, we are currently investigating the activation of glutamate receptor N-methyl-d-aspartate receptor (NMDAR) as the molecular mechanism for HHcy-induced BRB dysfunction. This review focuses on the studied effects of HHcy on BRB and the controversial role of HHcy in the pathogenesis of aging neurological diseases such as DR, AMD, and AD. We also highlight the possible mechanisms for such deleterious effects of HHcy.


2021 ◽  
Author(s):  
Shucheng Si ◽  
Fuzhong Xue ◽  
Kai Zhang

Abstract Background: Cytokines have been implicated in the initiation of human complex diseases, and the causality between cytokines and human phenotypes has not been systematically explored.Methods: Bidirectional mendelian randomization (MR) and multivariate mendelian randomization (MVMR) with Bayesian model averaging (MR-BMA) were performed to explore the causality of 41 cytokines and 83 human phenotypes.Results: Inverse variance weighted (IVW) MR showed that MIG, SCGFb, SCF, and MIF had causal effects on ovarian, colon, breast cancer, and their subtypes. Similarly, MCP1, TRAIL, and SCGFb had causal effects on heart failure (HF), stroke and its subtypes, coronary heart disease (CHD), and myocardial infarction (MI). About neurological diseases: MIP1b had positively causal effects on Alzheimer's disease (AD) and Parkinson's disease (PD), and MIG increased the risk of AD. MR-BMA showed that MIP1b was the top priority risk factor for AD and PD; MCP1 was the top risk factor for HF, stroke, and gout; SCF was the top risk factor for ovarian cancer; PDGFbb and SCGFb were the top risk factor for ischemic stroke (IS) (cardioembolic) and type 1 diabetes, respectively. The results of bidirectional MR showed endocrine diseases and autoimmune diseases influenced the circulating levels of cytokines.Conclusions: Our findings showed that cytokines have extensive causal effects on human complex diseases. Chemokines (MCP1, MIP1b) and growth factors (PDGFbb, SCGFb, SCF) could be recommended as valuable biomarkers of chronic diseases.


Function ◽  
2021 ◽  
Vol 2 (2) ◽  
Author(s):  
Maosheng Xia ◽  
Shanshan Liang ◽  
Shuai Li ◽  
Ming Ji ◽  
Beina Chen ◽  
...  

Abstract Metal implants are used worldwide, with millions of nails, plates, and fixtures grafted during orthopedic surgeries. Iron is the most common element of these metal implants. As time passes, implants can be corroded and iron can be released. Ionized iron permeates the surrounding tissues and enters circulation; importantly, iron ions pass through the blood–brain barrier. Can iron from implants represent a risk factor for neurological diseases? This remains an unanswered question. In this study, we discovered that patients with metal implants delivered through orthopedic surgeries have higher incidence of Parkinson’s disease or ischemic stroke compared to patients who underwent similar surgeries but did not have implants. Concentration of serum iron and ferritin was increased in subjects with metal implants. In experiments in vivo, we found that injection of iron dextran selectively decreased the presence of divalent metal transporter 1 (DMT1) in neurons through increasing the expression of Ndfip1, which degrades DMT1 and does not exist in glial cells. At the same time, excess of iron increased expression of DMT1 in astrocytes and microglial cells and triggered reactive astrogliosis and microgliosis. Facing the attack of excess iron, glial cells act as neuroprotectors to accumulate more extracellular iron by upregulating DMT1, whereas neurons limit iron uptake through increasing DMT1 degradation. Cerebral accumulation of iron in animals is associated with impaired cognition, locomotion, and mood. Excess iron from surgical implants thus can affect neural cells and may be regarded as a risk factor for neurodegeneration.


2021 ◽  
Author(s):  
Mariana Silva Regadas ◽  
Guilherme Albuquerque de Araújo Costa ◽  
Myrela Murad Sampaio

Background: COVID-19 patients with chronic diseases and comorbidities are more susceptible to the severe form of the infection. Neurological symptoms are reported by some patients infected by the virus and research seeks the relationship between the virus and neurological diseases, such as Parkinson’s Disease (PD). Objectives: To understand how COVID-19 and its effects affect patients with PD. Methods: Integrative review with search on Google Scholar, Scielo, PubMed and Science Direct platforms through an online scenario, selected articles from the years 2020 and 2021. Results: SARS-CoV-2 frequently undergo mutations, causes damage and inflammation. There are reports of symptoms such as anosmia, ageusia and headache. Anosmia stands out for its relationship with one initial symptom of PD, hyposmia. As the majority of PD patients are elderly and have comorbidities, there is a higher risk of being infected. Some patients with PD infected by the virus report worsening in motor and non-motor symptoms and such worsening can occur due to systemic inflammation, stress and the measures to contain the pandemic. Conclusions: PD is not a risk factor for COVID-19, however patients may experience worsening symptoms due to comorbidities, old age and stress caused by the pandemic. Strategies that reduce stress are options for maintaining the health of patients with PD.


ICAME 2007 ◽  
2008 ◽  
pp. 31-44
Author(s):  
Jolanta Galazka-Friedman

2008 ◽  
Vol 55 (1) ◽  
pp. 119-126 ◽  
Author(s):  
Wojciech Sawuła ◽  
Zyta Banecka-Majkutewicz ◽  
Leszek Kadziński ◽  
Joanna Jakóbkiewicz-Banecka ◽  
Grzegorz Wegrzyn ◽  
...  

Recent clinical research has pointed at hyperhomocysteinemia as an independent risk factor in a number of cardiovascular and neurological diseases. We have improved a chromatographic method of total plasma homocysteine measurements in order to obtain higher sensitivity, reliability and reproducibility. The method demonstrates excellent linearity (R=0.999), range (


2021 ◽  
Author(s):  
Deborah Lynn Parent

The recently developed Diffusion Gradient in Thin-films (DGT) technique is based on a simple device that accumulates metals in situ, over time in a Na resin gel. Metal ions diffuse through a hydrogel membrane and are rapidly bound by the resin. The many advantages associated with the DGT technique (simplicity, in situ technique, low detection limits, and ability to measure many metals) have lead to its rapid application in aquatic environments. Caveats have been recognized with the DGT technique when it is used in aquatic environments. These include: the ability of strongly complexed organic-metal molecules to diffuse through the hydrogel and become complexed by the resin gel, and in freshwater lakes with a low concentration of cations (Σ [cations] ≤ 2 × 10 -4 M), it is hypothesized that the diffusion coefficient of metal ions entering the DGT device increases. Both of these caveats overestimate the concentrations of labile inorganic metals in the deployment solution. The hypothesis that deploying DGT devices equipped with two different hydrogel formulations ("open" and "tight") will provide reasonable measurements of DGT-labile "organic" and "inorganic" concentrations of Mn, Cd and Pb was tested in the field. DGT devices were deployed in three lakes (Lake Tantare, Lake 8t. Joseph and Lake Memphremagog). To compare the responses of the DGT devices with the total dissolved metal concentration (< 0.20 um) of each lake, in situ dialysis samplers were deployed simultaneously. Overestimation of DGT-labile "inorganic" concentrations of Mn and Pb, and overestimation of DGT-labile "organic" Cd was observed when compared to the measured total dissolved metal concentrations in the lakes. The hypothesis that DGT devices equipped with a Ca form of the resin gel (as an alternative to the sodium based resin gel in the DGT device) will reasonably measure Mn, Cd and Pb labile metal concentrations in freshwater lakes with low cation concentrations was tested. DGT devices with the Ca form of the resin gel were deployed in Lake Tantare, Lake 8t. Joseph and Lake Memphremagog. Overestimation of DGT-labile metal concentrations of Mn, Cd and Pb were observed with the Ca resin gel in the lakes when compared to the measured total dissolved concentrations. The implication of these findings is that the DGT technique should not be used in freshwaters with low cation concentrations (Σ [cations] ≤ 2 × 10 -4 M), typical of lakes found in the Canadian environment, until the caveats of the technique have been resolved. Extreme caution should be used when drawing conclusions regarding the concentrations of inorganic and organic metal species, since it has been found the DGT devices with the two different hydrogel formulations overestimate the inorganic metal concentration relative to the organic metal concentration in aquatic environments.


Sign in / Sign up

Export Citation Format

Share Document