Effects of radiation and manganese oxide nanoparticles on human glioblastoma cell line U-87 MG glycolysis

Gliomas are the most common type of malignant brain tumors. Standard treatment of gliomas consists of surgical excision of the tumor with subsequent chemotherapy and radiotherapy. Tumor cells are characterized by rapid division with an increased uptake of glucose and its catabolism during glycolysis. To maintain rapid division, the level of glycolysis of the tumor cell is significantly increased, compared with normal cells. It is known that some nanoparticles (NP) have the property of accumulating in tumors. In particular, NPs of manganese oxide can penetrate into the brain and, with considerable accumulation, cause toxic effects. These facts served as a prerequisite for studying the effects of manganese oxide NPs on the viability of glioma cells. The purpose of this work was to study the effects of manganese oxide NPs, as well as their combination with gamma irradiation on the glycolysis of glioma cells. The cells were irradiated using the research radiobiological gamma-installation IGUR-1 based on 137Cs. The level of cell glycolysis was determined using the standard glycolytic stress test on a Seahorse XFp platform. Cell viability was determined using the ViaCount reagent staining of living and dead cells. Their count was performed using flow cytometry. We showed that the glycolysis of U-87 MG glioma cells was significantly reduced when incubated for 48 hours with manganese oxide NPs. Irradiation in combination with NPs or alone did not have significant effects on glycolysis of gliomas. Glioma incubation with manganese oxide NPs for 72 hours led to a significant reduction in cell viability. This study may be useful for the development of new therapies and diagnosis of gliomas

Author Correction: Elucidating causative gene variants in hereditary Parkinson’s disease in the Global Parkinson’s Genetics Program (GP2)

Correction to: npj Parkinson’s Disease, published online 27 June 2023 In this article the Global Parkinson’s Genetics Program (GP2) members names and affiliations were missing in the main author list of the Original article which are listed in the below

Defining the causes of sporadic Parkinson’s disease in the global Parkinson’s genetics program (GP2)

\ua9 2023, Springer Nature Limited. The Global Parkinson’s Genetics Program (GP2) will genotype over 150,000 participants from around the world, and integrate genetic and clinical data for use in large-scale analyses to dramatically expand our understanding of the genetic architecture of PD. This report details the workflow for cohort integration into the complex arm of GP2, and together with our outline of the monogenic hub in a companion paper, provides a generalizable blueprint for establishing large scale collaborative research consortia

Multi-ancestry genome-wide association meta-analysis of Parkinson’s disease

\ua9 2023, This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply. Although over 90 independent risk variants have been identified for Parkinson’s disease using genome-wide association studies, most studies have been performed in just one population at a time. Here we performed a large-scale multi-ancestry meta-analysis of Parkinson’s disease with 49,049 cases, 18,785 proxy cases and 2,458,063 controls including individuals of European, East Asian, Latin American and African ancestry. In a meta-analysis, we identified 78 independent genome-wide significant loci, including 12 potentially novel loci (MTF2, PIK3CA, ADD1, SYBU, IRS2, USP8, PIGL, FASN, MYLK2, USP25, EP300 and PPP6R2) and fine-mapped 6 putative causal variants at 6 known PD loci. By combining our results with publicly available eQTL data, we identified 25 putative risk genes in these novel loci whose expression is associated with PD risk. This work lays the groundwork for future efforts aimed at identifying PD loci in non-European populations

Effects of a compound from the group of substituted thiadiazines with hypothermia inducing properties on brain metabolism in rats, a study <i>in vivo</i> and <i>in vitro</i>

<div><p>The aim of the present study was to examine how administration of a compound of 1,3,4- thiadiazine class 2-morpholino-5-phenyl-6H-1,3,4-thiadiazine, hydrobromide (L-17) with hypothermia inducing properties affects the brain metabolism. The mechanism by which L-17 induces hypothermia is unknown; it may involve hypothalamic central thermoregulation as well as act via inhibition of energy metabolism. We tested the hypothesis that L-17 may induce hypothermia by directly inhibiting energy metabolism. The study <i>in vivo</i> was carried out on Sprague-Dawley adult rats. Two doses of L-17 were administered (190 mg/kg and 760 mg/kg). Brain metabolites were analyzed in control and treated groups using magnetic resonance spectroscopy, along with blood flow rate measurements in carotid arteries and body temperature measurements. Further <i>in vitro</i> studies on primary cultures from rat hippocampus were carried out to perform a mitochondria function test of L-17 pre-incubation (100 μM, 30 min). Analysis of brain metabolites showed no significant changes in 190 mg/kg treated group along with a significant reduction in body temperature by 1.5°C. However, administration of L-17 in higher dose 760 mg/kg provoked changes in brain metabolites indicative of neurotoxicity as well as reduction in carotid arteries flow rate. In addition, a balance change of excitatory and inhibitory neurotransmitters was observed. The L-17 pre-incubation with cell primary cultures from rat brain showed no significant changes in mitochondrial function. The results obtained in the study indicate that acute administration of L-17 190 mg/kg in rats induces mild hypothermia with no adverse effects onto brain metabolism.</p></div

Correlations of individual metabolites with the integral characteristics of metabolic patterns (the values of the Y₁) in rat brain cortex (A); values of the Y₁ in rat brain cortex (B).

<p>PEA—phosphorylethanolamine; Lac—lactate; Gly—glycine; Tau—taurine; Ins—myo-inositol; Glu—glutamic acid; Gln—glutamine; Cr—creatine; PCr—Phosphocreatine; Cho—choline; Asp—aspartate; Ala—alanine; GABA—gamma-aminobutyric acid; NAA—N-acetylaspartate.</p

Respiration (OCR) is measured under basal conditions and in response to mitochondrial inhibitors (Oligomycin (Olig), FCCP, Rotenone/Antimycine A (Rot)) in (A) mixed neuron and astrocyte culture (n = 9) and in (B) astrocyte culture (n = 9).

<p>Dashed line—control, solid line—L-17 pre-incubation. No significant differences in basal respiration or in mitochondrial stress test assessment were observed in L-17 (100 μM, pre-treated 30 min) cell cultures compared with control.</p