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Melatonin Provides Neuroprotection Following Traumatic Brain Injury-Promoted Mitochondrial Perturbation in Wistar Rat
- Source :
- Cellular and Molecular Neurobiology. 41:765-781
- Publication Year :
- 2020
- Publisher :
- Springer Science and Business Media LLC, 2020.
-
Abstract
- Excessive mitochondrial fission has been implicated in the etiology of neuronal cell death in traumatic brain injury (TBI). In the present study, we examined the efficacy of melatonin (Mel) as a neuroprotective agent against TBI-induced oxidative damage and mitochondrial dysfunction. We assessed the impact of Mel post-treatment (10 mg/kg b.wt., i.p.) at different time intervals in TBI-subjected Wistar rats. We found that the Mel treatment significantly attenuated brain edema, oxidative damage, mitochondrial fission, and promoted mitochondrial fusion. Additionally, Mel-treated rats showed restoration of mitochondrial membrane potential and oxidative phosphorylation with a concomitant reduction in cytochrome-c release. Further, Mel treatment significantly inhibited the translocation of Bax and Drp1 proteins to mitochondria in TBI-subjected rats. The restorative role of Mel treatment in TBI rats was supported by the mitochondrial ultra-structural analysis, which showed activation of mitochondrial fusion mechanism. Mel enhanced mitochondrial biogenesis by upregulation of PGC-1α protein. Our results demonstrated the remedial role of Mel in ameliorating mitochondrial dysfunctions that are modulated in TBI-subjected rats and provided support for mitochondrial-mediated neuroprotection as a putative therapeutic agent in the brain trauma.
- Subjects :
- Dynamins
Male
0301 basic medicine
Programmed cell death
Brain Edema
Oxidative phosphorylation
Mitochondrion
Pharmacology
Mitochondrial Dynamics
Models, Biological
Neuroprotection
Oxidative Phosphorylation
Mitochondrial Proteins
Melatonin
03 medical and health sciences
Cellular and Molecular Neuroscience
0302 clinical medicine
hemic and lymphatic diseases
Brain Injuries, Traumatic
Animals
Medicine
Rats, Wistar
neoplasms
bcl-2-Associated X Protein
Membrane Potential, Mitochondrial
Neurons
Behavior, Animal
Caspase 3
business.industry
Cytochromes c
Cell Biology
General Medicine
Mitochondrial Proton-Translocating ATPases
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
Mitochondria
Oxidative Stress
030104 developmental biology
Mitochondrial biogenesis
mitochondrial fusion
Mitochondrial fission
business
030217 neurology & neurosurgery
medicine.drug
Subjects
Details
- ISSN :
- 15736830 and 02724340
- Volume :
- 41
- Database :
- OpenAIRE
- Journal :
- Cellular and Molecular Neurobiology
- Accession number :
- edsair.doi.dedup.....d3db39454db22a06ffaae4efb6a7e5de
- Full Text :
- https://doi.org/10.1007/s10571-020-00884-5