Analiza stężenia wybranych neuroprzekaźników w surowicy chorych z zespołem Tourette'a

Background and purpose Metabolic disturbances of excitatory and inhibitory neurotransmitters are implicated in pathogenesis of Tourette syndrome (TS). The aim of the study was to measure serum concentrations of glutamic acid, γ-aminobutyric acid (GABA) and glycine in TS patients and evaluate any correlation between neurotransmitter levels and age at onset, actual age, gender, tic severity, duration of the disease and concomitant psychiatric disorders. Material and methods Sixty-seven TS patients, aged 16–59, and 57 healthy controls, aged 19–37, were enrolled in the study. Information regarding medical history and physical investigation was collected using a short questionnaire. Sixty-seven percent of patients were medication-free at the time of examination and the rest had withheld treatment for 24 hours before. Blood samples were taken after a 12-hour fasting period. HPLC technique was used. Results The TS group had higher glutamic acid and lower GABA levels. Glycine concentrations were comparable. No differences regarding neurotransmitter concentrations between treated and non-treated patients were found. Patients with concomitant obsessive-compulsive disorder and severe tics had higher glutamate levels. Glutamate concentrations correlated positively with the number of comorbid psychiatric disorders and GABA concentrations correlated negatively with the number of behavioural problems in patients with comorbidities. There was no correlation between analysed neurochemicals and age, gender, age at onset or disease duration. Conclusions Imbalance between excitatory and inhibitory systems in the brains of TS patients may be reflected by glutamate and GABA serum level changes. Glutamate and GABA may be biomarkers of the disease and high concentration of glutamate may indicate more severe course of TS.Wstęp i cel pracy Zaburzenia metabolizmu neuroprzekaźników pobudzających i hamujących odgrywają rolę w patogenezie zespołu Tourette'a. Celem pracy była analiza stężenia kwasu glutaminowego, γ-aminomasłowego (GABA) i glicyny w surowicy chorych z zespołem Tourette'a oraz ocena zależności pomiędzy stężeniami neurotransmiterów a wiekiem lub płcią, wiekiem w chwili zachorowania, nasileniem tików, czasem trwania choroby i współistniejącymi zaburzeniami psychiatrycznymi. Materiał i metody Zbadano 67 chorych na zespół Tourette'a w wieku 16–59 lat oraz 57 zdrowych osób w wieku 19–37 lat. Wykorzystano ankietę obejmującą informacje z badania podmiotowego i przedmiotowego. Sześćdziesiąt siedem procent chorych nie przyjmowało żadnych leków w momencie badania, u pozostałych wstrzymano podawanie 24 godziny przed pobraniem krwi. Próbki zebrano po 12-godzinnym okresie na czczo. Oznaczeń dokonano metodą HPLC. Wyniki W grupie chorych stężenie kwasu glutaminowego było większe, zaś GABA – mniejsze. Stężenie glicyny było podobne. Nie stwierdzono istotnej różnicy stężeń neuroprzekaźników pomiędzy grupą osób leczonych i nieleczonych. W grupie osób ze współistniejącym zaburzeniem obsesyjno–kompulsywnym oraz ciężkim nasileniem tików stężenie kwasu glutaminowego było większe. Stwierdzono dodatnią korelację pomiędzy stężeniem kwasu glutaminowego a liczbą dodatkowych zaburzeń psychiatrycznych oraz odwrotną kore-lację pomiędzy stężeniem GABA a liczbą zaburzeń behawioralnych w grupie ze współistniejącymi zaburzeniami psychiatrycznymi. Nie stwierdzono korelacji pomiędzy stężeniami analizowanych neuroprzekaźników a wiekiem lub płcią pacjentów, wiekiem zachorowania ani czasem trwania choroby. Wnioski Zaburzenie równowagi pomiędzy układem pobudzającym i hamującym w mózgu chorych z zespołem Tourette'a może się manifestować zmianami stężeń kwasu glutaminowego i GABA w surowicy. Kwas glutaminowy i GABA mogą być markerami choroby, a duże stężenie glutaminianu we krwi chorych może oznaczać cięższy przebieg zespołu Tourette'a

Mice with Mutation in Dynein Heavy Chain 1 Do Not Share the Same Tau Expression Pattern with Mice with SOD1-Related Motor Neuron Disease

Due to controversy about the involvement of Dync1h1 mutation in pathogenesis of motor neuron disease, we investigated expression of tau protein in transgenic hybrid mice with Dync1h1 (so-called Cra1/+), SOD1G93A (SOD1/+), double (Cra1/SOD1) mutations and wild-type controls. Total tau-mRNA and isoforms 0, 1 and 2 N expression was studied in frontal cortex, hippocampus, spinal cord and cerebellum of presymptomatic and symptomatic animals (age 70, 140 and 365 days). The most significant differences were found in brain cortex and cerebellum, but not in hippocampus and spinal cord. There were less changes in Cra1/SOD1 double heterozygotes compared to mice harboring single mutations. The differences in total tau expression and in profile of its isoforms between Cra1/+ and SOD1/+ transgenics indicate a distinct pathogenic entity of these two conditions

ERCC1-deficient cells and mice are hypersensitive to lipid peroxidation

Lipid peroxidation (LPO) products are relatively stable and abundant metabolites, which accumulate in tissues of mammals with aging, being able to modify all cellular nucleophiles, creating protein and DNA adducts including crosslinks. Here, we used cells and mice deficient in the ERCC1-XPF endonuclease required for nucleotide excision repair and the repair of DNA interstrand crosslinks to ask if specifically LPO-induced DNA damage contributes to loss of cell and tissue homeostasis. Ercc1-/- mouse embryonic fibroblasts were more sensitive than wild-type (WT) cells to the LPO products: 4-hydroxy-2-nonenal (HNE), crotonaldehyde and malondialdehyde. ERCC1-XPF hypomorphic mice were hypersensitive to CCl4 and a diet rich in polyunsaturated fatty acids, two potent inducers of endogenous LPO. To gain insight into the mechanism of how LPO influences DNA repair-deficient cells, we measured the impact of the major endogenous LPO product, HNE, on WT and Ercc1-/- cells. HNE inhibited proliferation, stimulated ROS and LPO formation, induced DNA base damage, strand breaks, error-prone translesion DNA synthesis and cellular senescence much more potently in Ercc1-/- cells than in DNA repair-competent control cells. HNE also deregulated base excision repair and energy production pathways. Our observations that ERCC1-deficient cells and mice are hypersensitive to LPO implicates LPO-induced DNA damage in contributing to cellular demise and tissue degeneration, notably even when the source of LPO is dietary polyunsaturated fats

Glutathione conjugation in male reproductive system: Studies on glutathione-S-transferase of bull and boar epididymis.

Male reproductive organs are extremely sensitive to the negative influence of toxic environmental factors as well as drugs, and until now not many attempts have been made at studying the detoxication enzymes and the relationship between the activity of those enzymes and spermatozoa fertility. In the present work we studied cytosolic glutathione-S-transferases (GST, EC 2.5.1.18) from different parts (head, corpus and tail) of bull and boar epididymis. We isolated two molecular forms of GST from each part of epididymis, characterized their biochemical properties and examined the mechanism of the catalyzed reaction. On the basis of their substrate specificity and isoelectric point, the isoforms were found to belong to the near neutral GST class mi. All examined GST forms exhibited higher affinity towards GSH than towards 1-chloro-2,4-dinitrobenzene (CDNB) and bull epididymis GST forms showed biphasic Lineweaver-Burk double reciprocal curves in the presence of GSH as a variable substrate. Boar epididymis anionic GST had the -SH groups both in the GSH and the CDNB binding place, whereas the cationic GST form - arginine residues in the CDNB binding place. Bull epididymis GST forms contained neither thiol nor arginine residues essential for catalytic activity