Neurochemical Journal最新文献

Abstract

D-ribose L-cysteine is a glutathione precursor that acts as an antioxidant. In the present study, we investigated the effect of D-ribose L-cysteine and L-dopa combination against paraquat toxicity in Drosophila melanogaster. Adult wild-type flies were exposed to Paraquat (500 μM), RLC (250 μM), and/or L-dopa (0.1 mM) in their diet for 7 days. The survival rate, locomotion activities, and markers of antioxidants (Catalase, glutathione-S-transferase, superoxide dismutase, thioredoxin reductase, total and non-protein thiol), oxidative stress (hydrogen peroxide, protein carbonyl, malondialdehyde, nitrite/nitrates), and dehydrogenase activity were measured in the flies. The results showed a non-toxic effect of the combination of RLC and L-dopa. In addition, elevated oxidative stress markers due to paraquat treatments were significantly reduced after treatments with RLC and L-dopa. Combination treatment also significantly restored altered antioxidant status, improved survival rate, and impaired locomotion induced by paraquat. This study suggests that RLC could serve as adjunct therapy with L-dopa in managing Parkinson’s disease and toxicity associated with paraquat and related compounds

Abstract

Recent studies have shown that sugammadex’s effects on the nervous system are controversial and its effect on nociception, morphine analgesia and tolerance is still unclear. The current study aimed to examine the possible involvement of sugammadex on nociception, morphine analgesia, and morphine tolerance development involving oxidative stress and NOD-like receptor protein 3 (NLRP3)/Interleukin-1β (IL-1β) signaling pathways in rats. The animals, thirty-six male Wistar Albino rats, were separated into six groups (n = 6 for each group): saline, sugammadex, morphine, morphine + sugammadex, morphine tolerance, and morphine tolerance + sugammadex. The analgesic effects were measured by analgesia tests (the tail-flick and hot plate). Oxidative stress parameters, NLRP3/IL-1β signaling pathway, and apoptotic proteins in the dorsal root ganglion (DRG) tissues were measured using Enzyme-Linked ImmunoSorbent Assay (ELISA) kits. Sugammadex had no antinociceptive activity when administered alone. However, it improved morphine’s analgesic efficacy and inhibited the development of morphine tolerance. In addition, it decreased oxidative stress and NLRP3/IL-1β signaling pathway proteins in the DRG when administered with single and repeated doses of morphine. Besides, sugammadex lowered apoptotic proteins in the DRG following tolerance development. Thus, we may conclude that the ability of sugammadex to affect morphine pharmacological activity may be mediated by the suppression of oxidative stress and the NLRP3/IL-1β pathway.

Abstract—The study was aimed at investigating the peculiarities of the conformational changes in serum albumin in patients with anxious and melancholic depression. Albumin conformation was measured by the method of the subnanosecond laser time resolved fluorescence spectroscopy. Anxious depression was accompanied by a significant decrease in the values of the three amplitudes of the serum albumin in comparison with controls. In the melancholic depression, the values of all three amplitudes of serum albumin molecules were significantly elevated in comparison with controls. These results clearly indicate that anxious and melancholic depression are accompanied by oppositely directed changes in serum albumin conformation.

Abstract

Delayed-onset biotinidase deficiency can mimic neuromyelitis optica spectrum disorders. We aimed to evaluate adult serum biotinidase activitiy in central nervous system idiopathic inflammatory demyelinating diseases. This cross-sectional study was conducted in our demyelinating diseases outpatient clinic between January and September 2021. Patients with diagnosis of multiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSD), radiologically isolated syndrome (RIS), or clinically isolated syndrome (CIS) were recruited. Patients’ demographic, clinical, laboratory, and radiological data were noted. Serum biotinidase activitiy were determined by enzymatic analysis. In line with the recommendation of the American College of Medical Genetic guide, the average adult biotidinase activity value was obtained in 100 healthy adults (9.61 nmol/mL/min) for our laboratory and this value was taken as a reference in our study. There were 187 participants (72% were female, mean age: 35.4 ± 9.3 years). In terms of biotinidase activity, there was no significant difference between MS, NMOSD, RIS, CIS (p = 0.249). The patients’ biotinidase activity (mean 8.61) was lower than the reference healthy adult activity (mean 9.61), and 68% (n = 128) of the patients had low biotidinase activity. There were no significant differences between patients with low (n = 128) or normal (n = 59) biotinidase activity for optic neuritis and myelitis (p = 0.408, p = 0.164). We found no correlation between biotinidase activitiy with expanded disability status scale scores and number of magnetic resonance imaging lesions. This study suggested that patients with idiopathic inflammatory demyelinating diseases have lower biotinidase activitiy than healthy people. Determination of biotinidase activitiy and appropriate supplementation of biotine could improve clinical outcomes.

Abstract—According to modern concepts, biochemical cascades activated in response to stress also contribute to cognitive functions, such as learning and memory formation. Considering a conditioned reflex as an adaptation to the external environment, one can assume its occurrence as a reaction to external challenges, which, when reinforced, contribute to the formation of a conditioned connection, and in the absence, cause the development of a stress response. The metabolic activity of the body is inextricably linked with circadian rhythms, which determine the daily fluctuations in light, temperature, oxygen content, and magnetic field. The integration of these timers is carried out by a protein of the cryptochrome family (CRY), which functions as a blue light receptor and is known as a repressor of the main circadian transcription complex CLOCK/BMAL1. In order to develop methods for non-invasive correction of pathologies of the nervous system on a model object of genetics, mutant strains of Drosophila are used to study the relationship between adaptive mechanisms of the formation of a conditioned connection and the development of a stress response to a weakening of the magnetic field, hypoxia and temperature changes. The data are discussed in light of the role of the CRY/CLOCK/BMAL1 system as a link in magnetoreception, hypoxia, circadian rhythm regulation, cognitive functions, and DNA double-strand breaks in nerve ganglia (an indicator of the physiological activity of neurons)

Abstract

Neuroblastoma is one of the most common and deadly childhood solid tumors. P-glycoprotein (P-gp) pump plays a role in developing resistance to many chemotherapeutic agents. The high expression of P-gp is associated with poor prognosis in drug resistance and neuroblastoma treatment. We aimed to evaluate the anticancer effect of Temozolomide (TMZ) on the SH-SY5Y human neuroblastoma cell line in the presence of P-gp inhibitor Verapamil (VER). In the present study, the antiproliferative effect of TMZ on SH-SY5Y cells alone and in combination with VER was evaluated using a colorimetric XTT viability test.SH-SY5Y cells were seeded to 96 well plates at 10 000 cells/well. TMZ (100 µM–10 mM) and VER (0.25–10 µg/mL) were applied to the cells alone first, then XTT measurements were performed after 24 and 48 h. In the study’s second phase, VER was applied to the cells at the fixed concentration of 2.5 µg/mL to block P-gp pumps, then increasing concentrations of TMZ were applied to the cells in the presence of VER. The current study showed that in addition to cytotoxic effects, VER + TMZ administration accelerated apoptosis in SH-SY5Y cells compared to TMZ utilization alone. The wound healing assay demonstrated that VER + TMZ combination also inhibited cell migration. Considering this evidence, combining TMZ with VER in the neuroblastoma cell line may inhibit migration and cell proliferation via the apoptosis pathway and produce a substantial anticancer effect.

Abstract—We studied the possibility of transferring exosomes of neural (NSC) and mesenchymal (MSC) mouse stem cells labeled with the fluorescent dye PKH26 into the cerebral cortex and hippocampus after their intranasal administration to mice, and the accumulation and localization of exosomes in cultured brain cells of various types, and also the effect of NSC and MSC exosomes on the parameters of the cell cycle and the level of apoptosis of cultured NSCs after irradiation at a dose of 4 Gy. The accumulation of exosomes obtained from the culture medium of NSCs and MSCs from the adipose tissue of C57BL/6 mice was shown both in the hippocampus and in the cerebral cortex after their intranasal administration to syngeneic mice. Exosomes were found predominantly in the perinuclear region of brain cells. In cultured NSCs and neurons and astrocytes differentiated from NSCs, exosomes were localized in the perinuclear region of cells and, in astrocytes, also in the cytoplasm. Exosomes accumulated most intensively in astrocytes. When studying the effect of stem cell exosomes on the cell cycle of irradiated NSCs, it was shown that the cultivation of NSCs irradiated at a dose of 4 Gy in the presence of exosomes of both NSCs and mouse MSCs did not lead to the restoration of cell cycle parameters but provided a decrease the number of apoptotic cells 24 h after exposure.

Abstract

Multiple neurological diseases are becoming increasingly common, posing a major public health concern around the world. The multifactorial pathophysiology of this debilitating disease, as well as the diverse effects of active constituents of microalgal medicine, as well as the drawbacks and lack of clinical treatments, may advocate for the discovery of new natural compounds with strong neuroprotective potential for treatment. Spirulina is a free-floating filamentous microalga that belongs to the cyanobacteria class and contains a variety of bioactive colored components such as C-phycocyanin (C-Pc), carotenoids, and chlorophyll. Modern pharmacological and molecular docking studies have demonstrated that Spirulina has disease-modifying therapeutic effects against these disorders, including neuroprotection, protein aggregate clearance, and neuroinflammation regulation. The study’s goal is to determine the benefits of Spirulina and its active constituents in the treatment of various neurodegenerative and neuropsychiatric diseases. This review summarizes evidence from in vitro, in vivo, and in silico research studies on neurological therapies focusing on the neuroprotective activities and molecular mechanisms of Spirulina and their active ingredients, with a focus on modulating various neurotransmitters and receptors, anti-inflammatory activities, anti-amyloid aggregation, and myelin sheath repair. The direct interaction between major active components of Spirulina sp. and orphan nuclear receptors, monoamine oxidase (MAO), bovine serum albumin (BSA), and pro-inflammatory proteins was modelled using molecular docking. This review’s findings support the use of Spirulina and its biologically active constituents as an alternative source of therapy for neurological diseases.

Abstract—There is no single model for the pathogenesis of schizophrenia, but neuroinflammation is considered a key mechanism in the development of this disease. The aim of our study was to analyze and summarize the literature data on the role of neuroinflammation markers in schizophrenia. We used the keywords “neuroinflammation,” “cytokines,” “chemokines,” “microcirculation,” “microglia,” “neurodestruction,” and “schizophrenia” to search for the articles published in 1990–2023 in the PubMed and e-Library.ru databases. The review discusses an integrated approach to the concept of neuroinflammation in schizophrenia with regard to known and promising markers. Studies, including those of the authors of the article, indicate a significant role of microcirculation disorders and endothelial dysfunction, cytokines and chemokines, and neurodestruction in the mechanisms of development and course of schizophrenia. The presented results require more detailed studies to establish new neurobiological and pathogenetic functions of neuroinflammation in schizophrenia.

Abstract—The aim of the study was to identify patterns of change in certain neurospecific proteins (BDNF, S100β, MBP) in the serum of patients with chronic mercury intoxication after stopping exposure to the toxicant. In clinical conditions, men with an established diagnosis of chronic mercury intoxication (CMI) were examined in a distant period after isolation from a toxicant in chemical production. Serum concentrations of neurospecific proteins (BDNF, S100β, MBP) were determined by solid-phase enzyme-linked immunosorbent assay using a commercial test-systems of ChemiKine (United States), CanAg (Sweden), and AnshLabs (United States), respectively. The obtained results indicate and confirm the progression of the disease in the distant, post-exposure period of chronic mercury intoxication, which corresponds to the clinical manifestation of the disease. Elevated serum concentrations of BDNF, S100β protein, and MBP were reported in patients with CMI 5 years after exposure to the toxicant. Long-lasting high levels of neurotrophic proteins may reflect the course of neurodestructive processes occurring in the nervous tissue and the progression of the disease. BDNF deficiency in CMI individuals examined in a linked sample at 8 years post-exposure may be indicative of attenuation of neurogenesis. Further studies will contribute to a more accurate definition and understanding of the use of serum concentrations of BDNF, S100β protein, MBP as markers of pathological process activity and a specific target for effective treatment.