Neuroprotective Mechanism of MOTS-c in TBI Mice: Insights from Integrated Transcriptomic and Metabolomic Analyses

References

• Timofeev I, Santarius T, Kolias AG, Hutchinson PJA. Decompressive craniectomy - operative technique and perioperative care. Adv Tech Stand Neurosurg. 2012;38:115–136. doi:10.1007/978-3-7091-0676-1_6
   PubMedGoogle Scholar
• Khellaf A, Khan DZ, Helmy A. Recent advances in traumatic brain injury. J Neurol. 2019;266(11):2878–2889. doi:10.1007/s00415-019-09541-4
   PubMed Web of Science ®Google Scholar
• Wong VS, Langley B. Epigenetic changes following traumatic brain injury and their implications for outcome, recovery and therapy. Neurosci Lett. 2016;625:26–33. doi:10.1016/j.neulet.2016.04.009
   PubMed Web of Science ®Google Scholar
• Hellewell SC, Yan EB, Agyapomaa DA, Bye N, Morganti-Kossmann MC. Post-traumatic hypoxia exacerbates brain tissue damage: analysis of axonal injury and glial responses. J Neurotrauma. 2010;27(11):1997–2010. doi:10.1089/neu.2009.1245
   PubMed Web of Science ®Google Scholar
• Simon DW, Mcgeachy MJ, Bayir H, Clark RS, Loane DJ, Kochanek PM. The far-reaching scope of neuroinflammation after traumatic brain injury. Nat Rev Neurol. 2017;13(3):171–191. doi:10.1038/nrneurol.2017.13
   PubMed Web of Science ®Google Scholar
• Johnson NH, De Rivero Vaccari JP, Bramlett HM, Keane RW, Dietrich WD. Inflammasome activation in traumatic brain injury and Alzheimer’s disease. Transl Res. 2023;254:1–12. doi:10.1016/j.trsl.2022.08.014
   PubMed Web of Science ®Google Scholar
• Firsching R, Rickels E, Mauer UM, et al. Guidelines for the treatment of head injury in adults. J Neurol Surg Cent Eur Neurosurg. 2017;78(5):478–487. doi:10.1055/s-0037-1599239
   PubMedGoogle Scholar
• Yue Z, Zhi X, Bi L, Zhao L, Ji J. Treatment and prognostic risk factors for intracranial infection after craniocerebral surgery. Neurosurg Rev. 2023;46(1):199. doi:10.1007/s10143-023-02106-0
   PubMed Web of Science ®Google Scholar
• Nishimura K, Sanchez-Molano J, Kerr N, et al. Beneficial effects of human Schwann cell-derived exosomes in mitigating secondary damage after penetrating ballistic-like brain injury. J Neurotrauma. 2024. doi:10.1089/neu.2023.0650
   Web of Science ®Google Scholar
• Lee C, Zeng J, Drew BG, et al. The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. Cell Metab. 2015;21(3):443–454. doi:10.1016/j.cmet.2015.02.009
   PubMed Web of Science ®Google Scholar
• Yin X, Jing Y, Chen Q, Abbas AB, Hu J, Xu H. The intraperitoneal administration of MOTS-c produces antinociceptive and anti-inflammatory effects through the activation of AMPK pathway in the mouse formalin test. Eur J Pharmacol. 2020;870:172909. doi:10.1016/j.ejphar.2020.172909
   PubMed Web of Science ®Google Scholar
• Kim S-J, Mehta HH, Wan J, et al. Mitochondrial peptides modulate mitochondrial function during cellular senescence. Aging. 2018;10(6):1239–1256. doi:10.18632/aging.101463
   PubMedGoogle Scholar
• Kim KH, Son JM, Benayoun BA, Lee C. The mitochondrial-encoded peptide MOTS-c translocates to the nucleus to regulate nuclear gene expression in response to metabolic stress. Cell Metab. 2018;28(3):516–524e7. doi:10.1016/j.cmet.2018.06.008
   PubMed Web of Science ®Google Scholar
• Zhai D, Ye Z, Jiang Y, et al. MOTS-c peptide increases survival and decreases bacterial load in mice infected with MRSA. Mol Immunol. 2017;92:151–160. doi:10.1016/j.molimm.2017.10.017
   PubMed Web of Science ®Google Scholar
• Jiang J, Chang X, Nie Y, et al. Peripheral administration of a cell-penetrating MOTS-c analogue enhances memory and attenuates Abeta(1-42)- or LPS-induced memory impairment through inhibiting neuroinflammation. ACS Chem Neurosci. 2021;12(9):1506–1518. doi:10.1021/acschemneuro.0c00782
   PubMed Web of Science ®Google Scholar
• Lowe R, Shirley N, Bleackley M, Dolan S, Shafee T. Transcriptomics technologies. PLoS Comput Biol. 2017;13(5):e1005457. doi:10.1371/journal.pcbi.1005457
   PubMed Web of Science ®Google Scholar
• Bujak R, Struck-Lewicka W, Markuszewski MJ, Kaliszan R. Metabolomics for laboratory diagnostics. J Pharm Biomed Anal. 2015;113:108–120. doi:10.1016/j.jpba.2014.12.017
   PubMed Web of Science ®Google Scholar
• Xiao X, Xu L, Lu H, et al. Untargeted metabolomic analyses of body fluids to differentiate TBI DOC and NTBI DOC. Curr Mol Med. 2023;24(9). doi:10.2174/0115665240249826230928104512
   Google Scholar
• Bartel J, Krumsiek J, Schramm K, et al. The human blood metabolome-transcriptome interface. PLoS Genet. 2015;11(6):e1005274. doi:10.1371/journal.pgen.1005274
   PubMed Web of Science ®Google Scholar
• Karczewski KJ, Snyder MP. Integrative omics for health and disease. Nat Rev Genet. 2018;19(5):299–310. doi:10.1038/nrg.2018.4
   PubMed Web of Science ®Google Scholar
• Heo YJ, Hwa C, Lee GH, Park JM, An JY. Integrative multi-omics approaches in cancer research: from biological networks to clinical subtypes. Mol Cells. 2021;44(7):433–443. doi:10.14348/molcells.2021.0042
   PubMed Web of Science ®Google Scholar
• Wang J, Li CL, Tu BJ, et al. Integrated epigenetics, transcriptomics, and metabolomics to analyze the mechanisms of Benzo[a]pyrene neurotoxicity in the hippocampus. Toxicol Sci. 2018;166(1):65–81. doi:10.1093/toxsci/kfy192
   PubMed Web of Science ®Google Scholar
• Li Z-Q, Wang -L-L, Zhou J, et al. Integration of transcriptomics and metabolomics profiling reveals the metabolic pathways affected in dictamnine-induced hepatotoxicity in mice. J Proteomics. 2020;213:103603. doi:10.1016/j.jprot.2019.103603
   PubMed Web of Science ®Google Scholar
• Zhu Y, Wu X, Liu Y, Zhang J, Lin D. Integration of transcriptomics and metabolomics reveals the responses of earthworms to the long-term exposure of TiO(2) nanoparticles in soil. Sci Total Environ. 2020;719:137492. doi:10.1016/j.scitotenv.2020.137492
   PubMed Web of Science ®Google Scholar
• Alluri H, Shaji CA, Davis ML, Tharakan B. A mouse controlled cortical impact model of traumatic brain injury for studying blood-brain barrier dysfunctions. Methods Mol Biol. 2018;1717:37–52.
   PubMedGoogle Scholar
• Albert-Weissenberger C, Sirén A-L. Experimental traumatic brain injury. Exp Transl Stroke Med. 2010;2(1):16. doi:10.1186/2040-7378-2-16
   PubMedGoogle Scholar
• Romine J, Gao X, Chen J, Controlled cortical impact model for traumatic brain injury. J Vis Exp. 2014;90:e51781. doi:10.3791/51781
   PubMed Web of Science ®Google Scholar
• Zempo H, Kim S-J, Fuku N, et al. A pro-diabetogenic mtDNA polymorphism in the mitochondrial derived peptide, MOTS-c. Aging. 2021;13(2):1692–1717. doi:10.18632/aging.202529
   PubMedGoogle Scholar
• Wu J, Xiao D, Yu K, Shalamu K, He B, Zhang M. The protective effect of the mitochondrial-derived peptide MOTS-c on LPS-induced septic cardiomyopathy. Acta Biochim Biophys Sin. 2023;55(2):285–294. doi:10.3724/abbs.2023006
   Google Scholar
• Ming W, Lu G, Xin S, et al. Mitochondria related peptide MOTS-c suppresses ovariectomy-induced bone loss via AMPK activation. Biochem Biophys Res Commun. 2016;476(4):412–419. doi:10.1016/j.bbrc.2016.05.135
   PubMed Web of Science ®Google Scholar
• Lu H, Wei M, Zhai Y, et al. MOTS-c peptide regulates adipose homeostasis to prevent ovariectomy-induced metabolic dysfunction. J Mol Med. 2019;97(4):473–485. doi:10.1007/s00109-018-01738-w
   PubMed Web of Science ®Google Scholar
• Marklund N. Rodent Models of Traumatic Brain Injury: methods and Challenges. Methods Mol Biol. 2016;1462:29–46.
   PubMedGoogle Scholar
• Navarro JC, Pillai S, Cherian L, Garcia R, Grill RJ, Robertson CS. Histopathological and behavioral effects of immediate and delayed hemorrhagic shock after mild traumatic brain injury in rats. J Neurotrauma. 2012;29(2):322–334. doi:10.1089/neu.2011.1979
   PubMed Web of Science ®Google Scholar
• Dewitt DS, Perez-Polo R, Hulsebosch CE, Dash PK, Robertson CS. Challenges in the development of rodent models of mild traumatic brain injury. J Neurotrauma. 2013;30(9):688–701. doi:10.1089/neu.2012.2349
   PubMed Web of Science ®Google Scholar
• Lee B, Sur BJ, Han JJ, et al. Krill phosphatidylserine improves learning and memory in Morris water maze in aged rats. Prog Neuropsychopharmacol Biol Psychiatry. 2010;34(6):1085–1093. doi:10.1016/j.pnpbp.2010.05.031
   PubMed Web of Science ®Google Scholar
• Ren S, Peng Z, Mao JH, et al. RNA-seq analysis of prostate cancer in the Chinese population identifies recurrent gene fusions, cancer-associated long noncoding RNAs and aberrant alternative splicings. Cell Res. 2012;22(5):806–821. doi:10.1038/cr.2012.30
   PubMed Web of Science ®Google Scholar
• Liu YW, Li S, Dai SS. Neutrophils in traumatic brain injury (TBI): friend or foe? J Neuroinflammation. 2018;15(1):146. doi:10.1186/s12974-018-1173-x
   PubMedGoogle Scholar
• Schindler CR, Lustenberger T, Woschek M, et al. Severe Traumatic Brain Injury (TBI) modulates the kinetic profile of the inflammatory response of markers for neuronal damage. J Clin Med. 2020;9(6):1667. doi:10.3390/jcm9061667
   PubMed Web of Science ®Google Scholar
• Cho CF, Wolfe JM, Fadzen CM, et al. Blood-brain-barrier spheroids as an in vitro screening platform for brain-penetrating agents. Nat Commun. 2017;8(1):15623. doi:10.1038/ncomms15623
   PubMedGoogle Scholar
• Guidotti G, Brambilla L, Rossi D. Cell-penetrating peptides: from basic research to clinics. Trends Pharmacol Sci. 2017;38(4):406–424. doi:10.1016/j.tips.2017.01.003
   PubMed Web of Science ®Google Scholar
• Böhmová E, Machová D, Pechar M, et al. Cell-penetrating peptides: a useful tool for the delivery of various cargoes into cells. Physiol Res. 2018;67:267–279. doi:10.33549/physiolres.933975
   PubMed Web of Science ®Google Scholar
• Bloom BR, Bennett B. Mechanism of a reaction in vitro associated with delayed-type hypersensitivity. Science. 1966;153(3731):80–82. doi:10.1126/science.153.3731.80
   PubMed Web of Science ®Google Scholar
• Nishihira J. Macrophage Migration Inhibitory Factor (MIF): its essential role in the immune system and cell growth. J Interferon Cytokine Res. 2000;20(9):751–762. doi:10.1089/10799900050151012
   PubMed Web of Science ®Google Scholar
• Zernecke A, Bernhagen J, Weber C. Macrophage migration inhibitory factor in cardiovascular disease. Circulation. 2008;117(12):1594–1602. doi:10.1161/CIRCULATIONAHA.107.729125
   PubMed Web of Science ®Google Scholar
• Nobre CC, De Araujo JM, Fernandes TA, et al. Macrophage Migration Inhibitory Factor (MIF): biological activities and relation with cancer. Pathol Oncol Res. 2017;23(2):235–244. doi:10.1007/s12253-016-0138-6
   PubMed Web of Science ®Google Scholar
• Nasiri E, Sankowski R, Dietrich H, et al. Key role of MIF-related neuroinflammation in neurodegeneration and cognitive impairment in Alzheimer’s disease. Mol Med. 2020;26(1):34. doi:10.1186/s10020-020-00163-5
   PubMed Web of Science ®Google Scholar
• Wang H, Qi W, Zou C, et al. NEK1-mediated retromer trafficking promotes blood-brain barrier integrity by regulating glucose metabolism and RIPK1 activation. Nat Commun. 2021;12(1):4826. doi:10.1038/s41467-021-25157-7
   PubMed Web of Science ®Google Scholar
• Mifflin L, Ofengeim D, Yuan J. Receptor-interacting protein kinase 1 (RIPK1) as a therapeutic target. Nat Rev Drug Discov. 2020;19(8):553–571. doi:10.1038/s41573-020-0071-y
   PubMed Web of Science ®Google Scholar
• Li Y, Zou C, Chen C, et al. Myeloid-derived MIF drives RIPK1-mediated cerebromicrovascular endothelial cell death to exacerbate ischemic brain injury. Proc Natl Acad Sci U S A. 2023;120(5):e2219091120. doi:10.1073/pnas.2219091120
   PubMed Web of Science ®Google Scholar
• Trigiani LJ, Bourourou M, Lacalle-Aurioles M, et al. A functional cerebral endothelium is necessary to protect against cognitive decline. J Cereb Blood Flow Metab. 2022;42(1):74–89. doi:10.1177/0271678X211045438
   PubMed Web of Science ®Google Scholar
• Nation DA, Sweeney MD, Montagne A, et al. Blood-brain barrier breakdown is an early biomarker of human cognitive dysfunction. Nat Med. 2019;25(2):270–276. doi:10.1038/s41591-018-0297-y
   PubMed Web of Science ®Google Scholar
• Montagne A, Nation DA, Sagare AP, et al. APOE4 leads to blood-brain barrier dysfunction predicting cognitive decline. Nature. 2020;581(7806):71–76. doi:10.1038/s41586-020-2247-3
   PubMed Web of Science ®Google Scholar
• Ushio-Fukai M, Alexander RW. Reactive oxygen species as mediators of angiogenesis signaling: role of NAD(P)H oxidase. Mol Cell Biochem. 2004;264(1–2):85–97. doi:10.1023/B:MCBI.0000044378.09409.b5
   PubMed Web of Science ®Google Scholar
• Touyz RM, Briones AM. Reactive oxygen species and vascular biology: implications in human hypertension. Hypertens Res. 2011;34(1):5–14. doi:10.1038/hr.2010.201
   PubMed Web of Science ®Google Scholar
• Tauffenberger A, Magistretti PJ. Reactive oxygen species: beyond their reactive behavior. Neurochem Res. 2021;46(1):77–87. doi:10.1007/s11064-020-03208-7
   PubMed Web of Science ®Google Scholar
• Zheng JY, Tan HL, Matsudaira PT, Choo A. Excess reactive oxygen species production mediates monoclonal antibody-induced human embryonic stem cell death via oncosis. Cell Death Differ. 2017;24(3):546–558. doi:10.1038/cdd.2016.164
   PubMed Web of Science ®Google Scholar
• Mach F, Steffens S. The role of the endocannabinoid system in atherosclerosis. J Neuroendocrinol. 2008;20(Suppl 1):53–57. doi:10.1111/j.1365-2826.2008.01685.x
   PubMedGoogle Scholar
• Matthews AT, Ross MK. Oxyradical stress, endocannabinoids, and atherosclerosis. Toxics. 2015;3(4):481–498. doi:10.3390/toxics3040481
   PubMedGoogle Scholar
• Coles JP. Regional ischemia after head injury. Curr Opin Crit Care. 2004;10(2):120–125. doi:10.1097/00075198-200404000-00008
   PubMedGoogle Scholar
• Demers-Marcil S, Coles JP. Cerebral metabolic derangements following traumatic brain injury. Curr Opin Anaesthesiol. 2022;35(5):562–569. doi:10.1097/ACO.0000000000001183
   PubMed Web of Science ®Google Scholar
• Xia Z, Zhou X, Li J, et al. Multiple-omics techniques reveal the role of glycerophospholipid metabolic pathway in the response of saccharomyces cerevisiae against hypoxic stress. Front Microbiol. 2019;10:1398. doi:10.3389/fmicb.2019.01398
   PubMed Web of Science ®Google Scholar