Abstract
Thioredoxin (TXN), encoded by Txn1, acts as a critical antioxidant in the defense against oxidative stress by regulating the dithiol/disulfide balance of interacting proteins. The role of TXN in the central nervous system (CNS) is largely unknown. A phenotype-driven study of N-ethyl-N-nitrosourea-mutated rats with running seizures at around five-week of age revealed the relevance of Txn1 mutations to CNS disorders. Genetic mapping identified Txn1-F54L in epileptic rats. The insulin-reducing activity of Txn1-F54L rats was approximately one-third that of the wild-type. Vacuolar degeneration in the midbrain, mainly in the thalamus and the inferior colliculus, was observed in the Txn1-F54L rats. The lesions displayed neuronal and oligodendrocyte cell death. Neurons in Txn1-F54L rats showed morphological changes in the mitochondria. Vacuolar degeneration began at three weeks of age, and spontaneous repair began at seven weeks; a dramatic change from cell death to repair occurred in the midbrain during a restricted period. In conclusion, Txn1 is essential for the development of the midbrain in juvenile rats.
Competing Interest Statement
The authors have declared no competing interest.
List of abbreviations
- CNS
- central nervous system;
- WT
- wild type;
- ROS
- reactive oxygen species
- NADPH
- Nicotinamide adenine dinucleotide phosphate;
- NOX
- NADPH oxidases;
- ENU
- N-ethyl-N-nitrosourea
- SOD
- superoxide dismutase;
- CAT
- catalase;
- HD
- Huntington’s disease;
- ALS
- amyotrophic lateral sclerosis;
- MS
- multiple sclerosis;
- GSH
- Glutathione;
- GPx
- glutathione peroxidase;
- Prdx
- peroxiredoxin
- Txn
- thioredoxin;
- MRI
- magnetic resonance imaging;
- 8-OHdG
- 8-hydroxy-2’-deoxyguanosine;
- 4-HNE
- 4-hydroxynonenal
- TUNEL
- Terminal deoxynucleotidyl transferase-mediated dUTP Nick End Labeling
- PBS
- phosphate-buffered saline;
- HE
- hematoxylin and eosin;
- KB
- Klüver-Barrera
- DAB
- 3,3’-diaminobenzidine;
- IHC
- immunohistochemistry;
- GFAP
- glial fibrillary acidic protein;
- GAPDH
- Glyceraldehyde 3-phosphate dehydrogenase
- TEM
- Transmission electron microscope;