| Autor: |
Sambon M; Laboratory of Neurophysiology, GIGA-Neurosciences, University of Liège, 4000 Liège, Belgium., Gorlova A; Department of Psychiatry and Neuropsychology, Maastricht University, 6200 MD Maastricht, The Netherlands.; Institute of Molecular Medicine Laboratory of Psychiatric Neurobiology and Department of Normal Physiology, Sechenov First Moscow State Medical University, 119991 Moscow, Russia., Demelenne A; Laboratory for the Analysis of Medicines, CIRM, Department of Pharmacy, University of Liège, 4000 Liège, Belgium., Alhama-Riba J; Laboratory of Neurophysiology, GIGA-Neurosciences, University of Liège, 4000 Liège, Belgium.; Faculty of Sciences, University of Girona, 17004 Girona, Spain., Coumans B; Laboratory of Molecular Regulation of Neurogenesis, GIGA-Stem Cell, University of Liège, 4000 Liège, Belgium., Lakaye B; Laboratory of Molecular Regulation of Neurogenesis, GIGA-Stem Cell, University of Liège, 4000 Liège, Belgium., Wins P; Laboratory of Neurophysiology, GIGA-Neurosciences, University of Liège, 4000 Liège, Belgium., Fillet M; Laboratory for the Analysis of Medicines, CIRM, Department of Pharmacy, University of Liège, 4000 Liège, Belgium., Anthony DC; Institute of Molecular Medicine Laboratory of Psychiatric Neurobiology and Department of Normal Physiology, Sechenov First Moscow State Medical University, 119991 Moscow, Russia.; Department of Pharmacology, Oxford University, Oxford OX1 3QT, UK., Strekalova T; Department of Psychiatry and Neuropsychology, Maastricht University, 6200 MD Maastricht, The Netherlands.; Institute of Molecular Medicine Laboratory of Psychiatric Neurobiology and Department of Normal Physiology, Sechenov First Moscow State Medical University, 119991 Moscow, Russia., Bettendorff L; Laboratory of Neurophysiology, GIGA-Neurosciences, University of Liège, 4000 Liège, Belgium. |
| Abstrakt: |
Thiamine precursors, the most studied being benfotiamine (BFT), have protective effects in mouse models of neurodegenerative diseases. BFT decreased oxidative stress and inflammation, two major characteristics of neurodegenerative diseases, in a neuroblastoma cell line (Neuro2a) and an immortalized brain microglial cell line (BV2). Here, we tested the potential antioxidant and anti-inflammatory effects of the hitherto unexplored derivative O,S-dibenzoylthiamine (DBT) in these two cell lines. We show that DBT protects Neuro2a cells against paraquat (PQ) toxicity by counteracting oxidative stress at low concentrations and increases the synthesis of reduced glutathione and NADPH in a Nrf2-independent manner. In BV2 cells activated by lipopolysaccharides (LPS), DBT significantly decreased inflammation by suppressing translocation of NF-κB to the nucleus. Our results also demonstrate the superiority of DBT over thiamine and other thiamine precursors, including BFT, in all of the in vitro models. Finally, we show that the chronic administration of DBT arrested motor dysfunction in FUS transgenic mice, a model of amyotrophic lateral sclerosis, and it reduced depressive-like behavior in a mouse model of ultrasound-induced stress in which it normalized oxidative stress marker levels in the brain. Together, our data suggest that DBT may have therapeutic potential for brain pathology associated with oxidative stress and inflammation by novel, coenzyme-independent mechanisms. |
