Acute exposure to acrylamide (ACR), a type-2 alkene, may lead to a ataxia, skeletal muscles weakness and numbness of the extremities in human and laboratory animals. In the present manuscript, ACR acute neurotoxicity has been characterized in adult zebrafish, a vertebrate model increasingly used in human neuropharmacology and toxicology research. At behavioral level, ACR-treated animals exhibited "depression-like" phenotype comorbid with anxiety behavior. At transcriptional level, ACR induced down-regulation of regeneration-associated genes and up-regulation of oligodendrocytes and reactive astrocytes markers, altering also the expression of genes involved in the presynaptic vesicle cycling. ACR induced also significant changes in zebrafish brain proteome and formed adducts with selected cysteine residues of specific proteins, some of them essential for the presynaptic function. Finally, the metabolomics analysis shows a depletion in the monoamine neurotransmitters, consistent with the comorbid depression and anxiety disorder, in the brain of the exposed fish.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5962567 | PMC |
| http://dx.doi.org/10.1038/s41598-018-26343-2 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
[Neurocytoprotection advances in reperfusion therapy].
Zh Nevrol Psikhiatr Im S S Korsakova
January 2025
Pirogov Russian National Research Medical University (Pirogov University), Moscow, Russia.
Acute stroke is the second leading cause of death and the third leading cause of disability in the world. Ischemic stroke (IS) the most common type of stroke. In acute cerebral ischemia, damage to the brain tissue is complex and includes blood-brain barrier (BBB) dysfunction, neuroinflammation, oxidative stress, activation of intracellular and extracellular signaling pathways, expression of neurotoxic agents, excitotoxicity, and apoptosis.
View Article and Find Full Text PDFMitochondrial targeted drug Dichloroacetate protects against sulfur mustard-induced neurotoxicity via the PDK/PDH axis and Akt/Nrf2 pathway.
Free Radic Biol Med
January 2025
Faculty of Naval Medicine, Naval Medical University, Shanghai, 200433, China.. Electronic address:
Sulfur mustard (SM) is a major toxic chemical threat to public health. Mitochondrial dysfunction is considered a critical contributing factor to mustard agent-induced damage. The brain is vulnerable to SM, which can lead to various types of acute and long-term psychiatric distress after exposure, but the neurotoxic mechanisms of SM, let alone drug candidates, are seldom studied.
View Article and Find Full Text PDFDysregulation of the Kynurenine Pathway in Relapsing Remitting Multiple Sclerosis and Its Correlations With Progressive Neurodegeneration.
Neurol Neuroimmunol Neuroinflamm
March 2025
Macquarie Medical School, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney.
Background And Objectives: Despite the absence of acute lesion activity in multiple sclerosis (MS), chronic neurodegeneration continues to progress, and a potential underlying mechanism could be the kynurenine pathway (KP). Prolonged activation of the KP from chronic inflammation is known to exacerbate the progression of neurodegenerative diseases through the production of neurotoxic metabolites. Among the 8 KP metabolites, six of them, namely kynurenine (KYN), 3-hydroxylkynurenine (3HK), anthranilic acid (AA), kynurenic acid (KYNA), and quinolinic acid (QUIN), have been associated with neurodegeneration.
View Article and Find Full Text PDFCD19-directed chimeric antigen receptor-engineered (CD19 CAR) T-cell therapy elicits high response rates but fails to induce durable responses in most adults with relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). In a previous clinical trial (NCT01865617), we observed anti-CAR immune responses associated with impaired in vivo CAR T-cell expansion after second infusions. Because these CD8+ T-cell responses were predominantly directed at peptides derived from the murine single chain variable fragment (scFv) in the CAR, we conducted a clinical trial investigating the safety and efficacy of CD19 CAR T-cells engineered with a CAR incorporating a fully human scFv (JCAR021) in adults with R/R B-ALL (NCT03103971).
View Article and Find Full Text PDFRole of procalcitonin, C reactive protein and ferritin in cytokine release syndrome after CAR T-cell therapy in children and young adults.
Biomarkers
January 2025
Pediatric Intensive Care Unit, Hospital Sant Joan de Déu-University of Barcelona, Barcelona, Spain.
PurposeChimeric antigen receptor (CAR) T-cell CD19 therapy has changed the treatment paradigm for patients with relapsed/refractory B-cell acute lymphoblastic leukemia. It is frequently associated with potentially severe toxicities: cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), and admission to PICU is often required. Some biomarkers seem to correlate with CRS severity.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!