Long-term effects of myo-inositol on traumatic brain injury: Epigenomic and transcriptomic studies
Background and purpose: Traumatic brain injury (TBI) and its consequences remain great challenges for neurology. Consequences of TBI are associated with various alterations in the brain but little is known about long-term changes of epigenetic DNA methylation patterns. Moreover, nothing is known abo...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-06-01
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| Series: | IBRO Neuroscience Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2667242124000137 |
| _version_ | 1827224324037148672 |
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| author | Nino Oganezovi Vincenzo Lagani Marine Kikvidze Georgi Gamkrelidze Lia Tsverava Eka Lepsveridze Kevin M. Kelly Revaz Solomonia |
| author_facet | Nino Oganezovi Vincenzo Lagani Marine Kikvidze Georgi Gamkrelidze Lia Tsverava Eka Lepsveridze Kevin M. Kelly Revaz Solomonia |
| author_sort | Nino Oganezovi |
| collection | DOAJ |
| description | Background and purpose: Traumatic brain injury (TBI) and its consequences remain great challenges for neurology. Consequences of TBI are associated with various alterations in the brain but little is known about long-term changes of epigenetic DNA methylation patterns. Moreover, nothing is known about potential treatments that can alter these epigenetic changes in beneficial ways. Therefore, we have examined myo-inositol (MI), which has positive effects on several pathological conditions. Methods: TBI was induced in mice by controlled cortical impact (CCI). One group of CCI animals received saline injections for two months (TBI+SAL), another CCI group received MI treatment (TBI+MI) for the same period and one group served as a sham-operated control. Mice were sacrificed 4 months after CCI and changes in DNA methylome and transcriptomes were examined. Results: For the first time we: (i) provide comprehensive map of long-term DNA methylation changes after CCI in the hippocampus; (ii) identify differences by methylation sites between the groups; (iii) characterize transcriptome changes; (iv) provide association between DNA methylation sites and gene expression. MI treatment is linked with upregulation of genes covering 33 biological processes, involved in immune response and inflammation. In support of these findings, we have shown that expression of BATF2, a transcription factor involved in immune-regulatory networks, is upregulated in the hippocampus of the TBI+MI group where the BATF2 gene is demethylated. Conclusion: TBI is followed by long-term epigenetic and transcriptomic changes in hippocampus. MI treatment has a significant effect on these processes by modulation of immune response and biological pathways of inflammation. |
| first_indexed | 2024-03-08T00:47:41Z |
| format | Article |
| id | doaj.art-0b122939eae24ca08fdff8f9155232da |
| institution | Directory Open Access Journal |
| issn | 2667-2421 |
| language | English |
| last_indexed | 2025-03-21T17:08:28Z |
| publishDate | 2024-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | IBRO Neuroscience Reports |
| spelling | doaj.art-0b122939eae24ca08fdff8f9155232da2024-06-14T05:46:40ZengElsevierIBRO Neuroscience Reports2667-24212024-06-0116291299Long-term effects of myo-inositol on traumatic brain injury: Epigenomic and transcriptomic studiesNino Oganezovi0Vincenzo Lagani1Marine Kikvidze2Georgi Gamkrelidze3Lia Tsverava4Eka Lepsveridze5Kevin M. Kelly6Revaz Solomonia7School of Natural Sciences and Medicine, Institute of Chemical Biology, Ilia State University, Tbilisi, GeorgiaSchool of Natural Sciences and Medicine, Institute of Chemical Biology, Ilia State University, Tbilisi, Georgia; Biological and Environmental Sciences and Engineering Division, King Abdullah University of Science and Technology, Thuwal 23955, Saudi ArabiaSchool of Natural Sciences and Medicine, Institute of Chemical Biology, Ilia State University, Tbilisi, GeorgiaSchool of Natural Sciences and Medicine, Institute of Chemical Biology, Ilia State University, Tbilisi, GeorgiaSchool of Natural Sciences and Medicine, Institute of Chemical Biology, Ilia State University, Tbilisi, Georgia; Iv. Beritashvili Centre of Experimental Biomedicine, Tbilisi, GeorgiaSchool of Natural Sciences and Medicine, Institute of Chemical Biology, Ilia State University, Tbilisi, GeorgiaDepartment of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA, United States; Department of Neurology, Philadelphia, PA, United States; Department of Neurology, Allegheny General Hospital, Pittsburgh, PA, United States; Center for Neuroscience Research, Allegheny Health Network Research Institute, Pittsburgh, PA, United States, Drexel University College of Medicine, Philadelphia, PA, United StatesSchool of Natural Sciences and Medicine, Institute of Chemical Biology, Ilia State University, Tbilisi, Georgia; Iv. Beritashvili Centre of Experimental Biomedicine, Tbilisi, Georgia; Corresponding author at: School of Natural Sciences and Medicine, Institute of Chemical Biology, Ilia State University, Tbilisi, Georgia.Background and purpose: Traumatic brain injury (TBI) and its consequences remain great challenges for neurology. Consequences of TBI are associated with various alterations in the brain but little is known about long-term changes of epigenetic DNA methylation patterns. Moreover, nothing is known about potential treatments that can alter these epigenetic changes in beneficial ways. Therefore, we have examined myo-inositol (MI), which has positive effects on several pathological conditions. Methods: TBI was induced in mice by controlled cortical impact (CCI). One group of CCI animals received saline injections for two months (TBI+SAL), another CCI group received MI treatment (TBI+MI) for the same period and one group served as a sham-operated control. Mice were sacrificed 4 months after CCI and changes in DNA methylome and transcriptomes were examined. Results: For the first time we: (i) provide comprehensive map of long-term DNA methylation changes after CCI in the hippocampus; (ii) identify differences by methylation sites between the groups; (iii) characterize transcriptome changes; (iv) provide association between DNA methylation sites and gene expression. MI treatment is linked with upregulation of genes covering 33 biological processes, involved in immune response and inflammation. In support of these findings, we have shown that expression of BATF2, a transcription factor involved in immune-regulatory networks, is upregulated in the hippocampus of the TBI+MI group where the BATF2 gene is demethylated. Conclusion: TBI is followed by long-term epigenetic and transcriptomic changes in hippocampus. MI treatment has a significant effect on these processes by modulation of immune response and biological pathways of inflammation.http://www.sciencedirect.com/science/article/pii/S2667242124000137Traumatic Brain InjuryDNA methylationGene expressionMyo-inositolBATF2 |
| spellingShingle | Nino Oganezovi Vincenzo Lagani Marine Kikvidze Georgi Gamkrelidze Lia Tsverava Eka Lepsveridze Kevin M. Kelly Revaz Solomonia Long-term effects of myo-inositol on traumatic brain injury: Epigenomic and transcriptomic studies IBRO Neuroscience Reports Traumatic Brain Injury DNA methylation Gene expression Myo-inositol BATF2 |
| title | Long-term effects of myo-inositol on traumatic brain injury: Epigenomic and transcriptomic studies |
| title_full | Long-term effects of myo-inositol on traumatic brain injury: Epigenomic and transcriptomic studies |
| title_fullStr | Long-term effects of myo-inositol on traumatic brain injury: Epigenomic and transcriptomic studies |
| title_full_unstemmed | Long-term effects of myo-inositol on traumatic brain injury: Epigenomic and transcriptomic studies |
| title_short | Long-term effects of myo-inositol on traumatic brain injury: Epigenomic and transcriptomic studies |
| title_sort | long term effects of myo inositol on traumatic brain injury epigenomic and transcriptomic studies |
| topic | Traumatic Brain Injury DNA methylation Gene expression Myo-inositol BATF2 |
| url | http://www.sciencedirect.com/science/article/pii/S2667242124000137 |
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