ArticleMolecular neurobiology2021
Epigenetic Blockade of Hippocampal SOD2 Via DNMT3b-Mediated DNA Methylation: Implications in Mild Traumatic Brain Injury-Induced Persistent Oxidative Damage.
Article in Molecular neurobiology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 28 citations in OpenAlex.
- From oxidative stress to epigenetic regulation: Molecular mechanisms of preterm brain injury and neuroprotective strategies (Review).Molecular medicine reports · 2026Review
- Dorsal raphe tau pathology disrupts sleep-wake orchestration and sleep architecture in a sex-specific manner.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Epigenetic mechanisms in traumatic brain injury: a focus on astrocytes and therapeutic implications.Journal of neuroinflammation · 2026Review
- The comparative ameliorating effects of an amorphous formula of curcumin and α-glycosyl isoquercitrin on hippocampal dysfunction in a rat gulf war illness model.Metabolic brain disease · 2026Article
- Environmental estrogens and animal reproductive health: mechanisms, biomarkers, and intervention approaches.Journal of animal science and biotechnology · 2026Review
- Selective reduction of KCNA4 in vulnerable glutamatergic-serotonin neurons of the dorsal raphe nucleus in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Deep Brain Stimulation of Lateral Habenula Ameliorates Depression-like Symptoms in Rats: Involvement of Mesolimbic Circuit.Neurochemical research · 2026Article
- HIGD1A Alleviates Oxidative Stress Related Ovarian Hypofunction by Enhancing Granulosa Cell Functions via NF-κB/SOD2 Signaling Pathway.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Mitochondrial Quality Control in Bovine Oocyte Maturation: Mechanisms, Challenges, and Prospects for Enhancing Reproductive Efficiency.Animals : an open access journal from MDPI · 2025Review
- The Role of Methylation Modification in Neural Injury and Repair.International journal of molecular sciences · 2025Review
- α-Lipoic acid alleviate myocardial infarction by suppressing age-independent macrophage senescence.Scientific reports · 2025Article
- Mild traumatic brain injury increases vulnerability to post-traumatic stress disorder in rats and the possible role of hippocampal DNA methylation.Frontiers in behavioral neuroscience · 2025Article
- Gut Microbiota Regulates Epigenetic Remodelling in the Amygdala: A Role in Repeated Mild Traumatic Brain Injury (rMTBI)-Induced Anxiety.Molecular neurobiology · 2024Article
- Curcumin can improve spinal cord injury by inhibiting DNA methylation.Molecular and cellular biochemistry · 2024Article
- Treatment effects of N-acetyl cysteine on resting-state functional MRI and cognitive performance in patients with chronic mild traumatic brain injury: a longitudinal study.Frontiers in neurology · 2024Article
- DNA Methylation-Mediated Mfn2 Gene Regulation in the Brain: A Role in Brain Trauma-Induced Mitochondrial Dysfunction and Memory Deficits.Cellular and molecular neurobiology · 2023Article
- The Applications and Mechanisms of Superoxide Dismutase in Medicine, Food, and Cosmetics.Antioxidants (Basel, Switzerland) · 2023Review
- Repeated ethanol exposure and withdrawal alters angiotensin-converting enzyme 2 expression in discrete brain regions: Implications for SARS-CoV-2 neuroinvasion.Alcohol, clinical & experimental research · 2023Article
- Traumatic brain injury-associated epigenetic changes and the risk for neurodegenerative diseases.Frontiers in neuroscience · 2023Article
- Repeated ethanol exposure and withdrawal alters ACE2 expression in discrete brain regions: Implications for SARS-CoV-2 infection.bioRxiv : the preprint server for biology · 2022Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
The recurrent events of mild trauma exacerbate the vulnerability for post-traumatic stress disorder; however, the underlying molecular mechanisms are scarcely known. The repeated mild traumatic brain injury (rMTBI) perturbs redox homeostasis which is primarily managed by superoxide dismutase 2 (SOD2). The current study investigates the role of DNA methylation in SOD2 gene regulation and its involvement in rMTBI-induced persistent neuropathology inflicted by weight drop injury paradigm. The oxidative damage, neurodegenerative indicators, and SOD2 function and its regulation in the hippocampus were analyzed after 48 h and 30 days of rMTBI. The temporal and episodic increase in ROS levels (oxidative stress) heightened 8-hydroxyguanosine levels indicating oxidative damage after rMTBI that was concomitant with decline in SOD2 function. In parallel, occupancy of DNMT3b at SOD2 promoter was higher post 30 days of the first episode of rMTBI causing hypermethylation at SOD2 promoter. This epigenetic silencing of SOD2 promoter was sustained after the second episode of rMTBI causing permanent blockade in SOD2 response. The resultant oxidative stress further culminated into the increasing number of degenerating neurons. The treatment with 5-azacytidine, a pan DNMT inhibitor, normalized DNA methylation levels and revived SOD2 function after the second episode of rMTBI. The release of blockade in SOD2 expression by DNMT inhibition also normalized the post-traumatic oxidative consequences and relieved the neurodegeneration and deficits in learning and memory as measured by novel object recognition test. In conclusion, DNMT3b-mediated DNA methylation plays a critical role in SOD2 gene regulation in the hippocampus, and the perturbations therein post rMTBI are detrimental to redox homeostasis manifesting into neurological consequences.
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