Skip to main content

Advertisement

Log in

The Ketogenic Diet but not Hydroxycitric Acid Keeps Brain Mitochondria Quality Control and mtDNA Integrity Under Focal Stroke

  • Published:
Molecular Neurobiology Aims and scope Submit manuscript

Abstract

Mitochondrial dysfunction in the ischemic brain is one of the hallmarks of stroke. Dietary interventions such as the ketogenic diet and hydroxycitric acid supplementation (a caloric restriction mimetic) may potentially protect neurons from mitochondrial damage induced by focal stroke in mice. We showed that in control mice, the ketogenic diet and the hydroxycitric acid did not impact significantly on the mtDNA integrity and expression of genes involved in the maintenance of mitochondrial quality control in the brain, liver, and kidney. The ketogenic diet changed the bacterial composition of the gut microbiome, which via the gut-brain axis may affect the increase in anxiety behavior and reduce mice mobility. The hydroxycitric acid causes mortality and suppresses mitochondrial biogenesis in the liver. Focal stroke modelling caused a significant decrease in the mtDNA copy number in both ipsilateral and contralateral brain cortex and increased the levels of mtDNA damage in the ipsilateral hemisphere. These alterations were accompanied by a decrease in the expression of some of the genes involved in maintaining mitochondrial quality control. The ketogenic diet consumption before stroke protects mtDNA in the ipsilateral cortex, probably via activation of the Nrf2 signaling. The hydroxycitric acid, on the contrary, increased stroke-induced injury. Thus, the ketogenic diet is the most preferred variant of dietetic intervention for stroke protection compared with the hydroxycitric acid supplementation. Our data confirm some reports about hydroxycitric acid toxicity, not only for the liver but also for the brain under stroke condition.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

Data Availability

The raw data are available from the corresponding author on request.

References

  1. Feigin VL, Brainin M, Norrving B, Martins S, Sacco RL, Hacke W, Fisher M, Pandian J, Lindsay P (2022) World Stroke Organization (WSO): Global Stroke Fact Sheet 2022. Int J Stroke 17:18–29. https://doi.org/10.1177/17474930211065917

    Article  PubMed  Google Scholar 

  2. Yang ZS, Mu J (2017) Co-administration of tissue plasminogen activator and hyperbaric oxygen in ischemic stroke: a continued promise for neuroprotection. Med Gas Res 7:68–73. https://doi.org/10.4103/2045-9912.202912

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Liu F, Lu J, Manaenko A, Tang J, Hu Q (2018) Mitochondria in ischemic stroke: new insight and implications. Aging Dis 9:924–937. https://doi.org/10.14336/AD.2017.1126

    Article  PubMed  PubMed Central  Google Scholar 

  4. Tian H, Chen X, Liao J, Yang T, Cheng S, Mei Z, Ge J (2022) Mitochondrial quality control in stroke: from the mechanisms to therapeutic potentials. J Cell Mol Med 26:1000–1012. https://doi.org/10.1111/jcmm.17189

    Article  PubMed  PubMed Central  Google Scholar 

  5. Ranjan AK, Briyal S, Gulati A (2020) Sovateltide (IRL-1620) activates neuronal differentiation and prevents mitochondrial dysfunction in adult mammalian brains following stroke. Sci Rep 10:12737. https://doi.org/10.1038/s41598-020-69673-w

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Zhou Y, Wang S, Li Y, Yu S, Zhao Y (2018) SIRT1/PGC-1α signaling promotes mitochondrial functional recovery and reduces apoptosis after intracerebral hemorrhage in rats. Front Mol Neurosci 10:443. https://doi.org/10.3389/fnmol.2017.00443

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Orgah JO, Ren J, Liu X, Orgah EA, Gao XM, Zhu Y (2019) Danhong injection facilitates recovery of post-stroke motion deficit via Parkin-enhanced mitochondrial function. Restor Neurol Neurosci 37:375–395. https://doi.org/10.3233/RNN-180828

    Article  CAS  PubMed  Google Scholar 

  8. Zhang Y, He Y, Wu M, Chen H, Zhang L, Yang D, Wang Q, Shen J (2020) Rehmapicroside ameliorates cerebral ischemia-reperfusion injury via attenuating peroxynitrite-mediated mitophagy activation. Free Radic Biol Med 160:526–539. https://doi.org/10.1016/j.freeradbiomed.2020.06.034

    Article  CAS  PubMed  Google Scholar 

  9. Chen Y, Guo S, Tang Y, Mou C, Hu X, Shao F, Yan W, Wu Q (2020) Mitochondrial fusion and fission in neuronal death induced by cerebral ischemia-reperfusion and its clinical application: a mini-review. Med Sci Monit 26:e928651. https://doi.org/10.12659/MSM.928651

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Szeto HH (2006) Mitochondria-targeted peptide antioxidants: novel neuroprotective agents. AAPS J 8:E521–E531. https://doi.org/10.1208/aapsj080362

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Silachev DN, Plotnikov EY, Pevzner IB, Zorova LD, Balakireva AV, Gulyaev MV, Pirogov YA, Skulachev VP, Zorov DB (2018) Neuroprotective effects of mitochondria-targeted plastoquinone in a rat model of neonatal hypoxic-ischemic brain injury. Molecules 23:1871. https://doi.org/10.3390/molecules23081871

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Wang S, Ma F, Huang L, Zhang Y, Peng Y, Xing C, Feng Y, Wang X, Peng Y (2018) Dl-3-n-Butylphthalide (NBP): a promising therapeutic agent for ischemic stroke. CNS Neurol Disord Drug Targets 17:338–347. https://doi.org/10.2174/1871527317666180612125843

    Article  CAS  PubMed  Google Scholar 

  13. Babenko VA, Silachev DN, Popkov VA, Zorova LD, Pevzner IB, Plotnikov EY, Sukhikh GT, Zorov DB (2018) Miro1 enhances mitochondria transfer from multipotent mesenchymal stem cells (MMSC) to neural cells and improves the efficacy of cell recovery. Molecules 23:687. https://doi.org/10.3390/molecules23030687

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Borlongan CV, Nguyen H, Lippert T, Russo E, Tuazon J, Xu K, Lee JY, Sanberg PR, Kaneko Y, Napoli E (2019) May the force be with you: transfer of healthy mitochondria from stem cells to stroke cells. J Cereb Blood Flow Metab 39:367–370. https://doi.org/10.1177/0271678X18811277

    Article  CAS  PubMed  Google Scholar 

  15. Xie Q, Zeng J, Zheng Y, Li T, Ren J, Chen K, Zhang Q, Xie R, Xu F, Zhu J (2021) Mitochondrial transplantation attenuates cerebral ischemia-reperfusion injury: possible involvement of mitochondrial component separation. Oxid Med Cell Longev 2021:1006636. https://doi.org/10.1155/2021/1006636

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Zorova LD, Popkov VA, Plotnikov EY, Silachev DN, Pevzner IB, Jankauskas SS, Babenko VA, Zorov SD, Balakireva AV, Juhaszova M, Sollott SJ, Zorov DB (2018) Mitochondrial membrane potential. Anal Biochem 552:50–59. https://doi.org/10.1016/j.ab.2017.07.009

    Article  CAS  PubMed  Google Scholar 

  17. Putti R, Sica R, Migliaccio V, Lionetti L (2015) Diet impact on mitochondrial bioenergetics and dynamics. Front Physiol 6:109. https://doi.org/10.3389/fphys.2015.00109

    Article  PubMed  PubMed Central  Google Scholar 

  18. Barry D, Ellul S, Watters L, Lee D, Haluska R Jr, White R (2018) The ketogenic diet in disease and development. Int J Dev Neurosci 68:53–58. https://doi.org/10.1016/j.ijdevneu.2018.04.005

    Article  PubMed  Google Scholar 

  19. Puchowicz MA, Zechel JL, Valerio J, Emancipator DS, Xu K, Pundik S, LaManna JC, Lust WD (2008) Neuroprotection in diet-induced ketotic rat brain after focal ischemia. J Cereb Blood Flow Metab 28:1907–1916. https://doi.org/10.1038/jcbfm.2008.79

    Article  CAS  PubMed  Google Scholar 

  20. Yang Q, Guo M, Wang X, Zhao Y, Zhao Q, Ding H, Dong Q, Cui M (2017) Ischemic preconditioning with a ketogenic diet improves brain ischemic tolerance through increased extracellular adenosine levels and hypoxia-inducible factors. Brain Res 1667:11–18. https://doi.org/10.1016/j.brainres.2017.04.010

    Article  CAS  PubMed  Google Scholar 

  21. Xu K, Ye L, Sharma K, Jin Y, Harrison MM, Caldwell T, Berthiaume JM, Luo Y, LaManna JC, Puchowicz MA (2017) Diet-induced ketosis protects against focal cerebral ischemia in mouse. Adv Exp Med Biol 977:205–213. https://doi.org/10.1007/978-3-319-55231-6_28

    Article  CAS  PubMed  Google Scholar 

  22. Guo M, Wang X, Zhao Y, Yang Q, Ding H, Dong Q, Chen X, Cui M (2018) Ketogenic diet improves brain ischemic tolerance and inhibits nlrp3 inflammasome activation by preventing Drp1-mediated mitochondrial fission and endoplasmic reticulum stress. Front Mol Neurosci 11:86. https://doi.org/10.3389/fnmol.2018.00086

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Manzanero S, Gelderblom M, Magnus T, Arumugam TV (2011) Calorie restriction and stroke. Exp Transl Stroke Med 3:8. https://doi.org/10.1186/2040-7378-3-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Hofer SJ, Carmona-Gutierrez D, Mueller MI, Madeo F (2022) The ups and downs of caloric restriction and fasting: from molecular effects to clinical application. EMBO Mol Med 14:e14418. https://doi.org/10.15252/emmm.202114418

    Article  CAS  PubMed  Google Scholar 

  25. Kyriazis M (2009) Calorie restriction mimetics: examples and mode of action. Open Longev Sci 3:17–21. https://doi.org/10.2174/1876326X00903010017

    Article  CAS  Google Scholar 

  26. Li L, Jiang Z, Yao Y, Yang Z, Ma H (2020) (-)-Hydroxycitric acid regulates energy metabolism by activation of AMPK - PGC1α - NRF1 signal pathway in primary chicken hepatocytes. Life Sci 254:117785. https://doi.org/10.1016/j.lfs.2020.117785

    Article  CAS  PubMed  Google Scholar 

  27. Ruiz Herrero J, Cañedo Villarroya E, García Peñas JJ, García Alcolea B, Gómez Fernández B, Puerta Macfarland LA, Pedrón Giner C (2020) Safety and effectiveness of the prolonged treatment of children with a ketogenic diet. Nutrients 12:306. https://doi.org/10.3390/nu12020306

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Andueza N, Giner RM, Portillo MP (2021) Risks associated with the use of Garcinia as a nutritional complement to lose weight. Nutrients 13:450. https://doi.org/10.3390/nu13020450

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. O’Callaghan TF, Ross RP, Stanton C, Clarke G (2016) The gut microbiome as a virtual endocrine organ with implications for farm and domestic animal endocrinology. Domest Anim Endocrinol 56(Suppl):S44–S55. https://doi.org/10.1016/j.domaniend.2016.05.003

    Article  CAS  PubMed  Google Scholar 

  30. Demidova TY, Lobanova KG, Oynotkinova OS (2020) Gut microbiota is an endocrine organ. Obes Metab 17:299–306. https://doi.org/10.14341/omet12457. (In Russ.)

    Article  Google Scholar 

  31. Watson BD, Dietrich WD, Busto R, Wachtel MS, Ginsberg MD (1985) Induction of reproducible brain infarction by photochemically initiated thrombosis. Ann Neurol 17:497–504. https://doi.org/10.1002/ana.410170513

    Article  CAS  PubMed  Google Scholar 

  32. Deacon RM (2011) Hyponeophagia: a measure of anxiety in the mouse. J Vis Exp 51:2613. https://doi.org/10.3791/2613

    Article  Google Scholar 

  33. Gureev AP, Shaforostova EA, Starkov AA, Popov VN (2018) β-guanidinopropionic acid stimulates brain mitochondria biogenesis and alters cognitive behavior in nondiseased mid-age mice. J Exp Neurosci 12:1179069518766524. https://doi.org/10.1177/1179069518766524

    Article  PubMed  PubMed Central  Google Scholar 

  34. Gureev AP, Shaforostova EA, Starkov AA, Popov VN (2017) Simplified qPCR method for detecting excessive mtDNA damage induced by exogenous factors. Toxicology 382:67–74. https://doi.org/10.1016/j.tox.2017.03.010

    Article  CAS  PubMed  Google Scholar 

  35. Kumar S, Stecher G, Li M, Knyaz C, Tamura K (2018) MEGA X: molecular evolutionary genetics analysis across computing platforms. Mol Biol Evol 35:1547–1549. https://doi.org/10.1093/molbev/msy096

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Wilder RJ (1921) The effects of ketonemia on the course of epilepsy. Mayo Clin Proc 2:307–308

    Google Scholar 

  37. Roberts MN, Wallace MA, Tomilov AA, Zhou Z, Marcotte GR, Tran D, Perez G, Gutierrez-Casado E, Koike S, Knotts TA, Imai DM, Griffey SM, Kim K, Hagopian K, McMackin MZ, Haj FG, Baar K, Cortopassi GA, Ramsey JJ, Lopez-Dominguez JA (2017) A ketogenic diet extends longevity and healthspan in adult mice. Cell Metab 26:539-546.e5. https://doi.org/10.1016/j.cmet.2017.08.005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Weber DD, Aminazdeh-Gohari S, Kofler B (2018) Ketogenic diet in cancer therapy. Aging 10:164–165. https://doi.org/10.18632/aging.101382

    Article  PubMed  PubMed Central  Google Scholar 

  39. Włodarek D (2019) Role of ketogenic diets in neurodegenerative diseases (Alzheimer’s disease and Parkinson’s disease). Nutrients 11:169. https://doi.org/10.3390/nu11010169

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Zhao Q, Stafstrom CE, Fu DD, Hu Y, Holmes GL (2004) Detrimental effects of the ketogenic diet on cognitive function in rats. Pediatr Res 55:498–506. https://doi.org/10.1203/01.PDR.0000112032.47575.D1

    Article  CAS  PubMed  Google Scholar 

  41. Murphy P, Likhodii SS, Hatamian M, McIntyre Burnham W (2005) Effect of the ketogenic diet on the activity level of Wistar rats. Pediatr Res 57:353–357. https://doi.org/10.1203/01.PDR.0000150804.18038.79

    Article  CAS  PubMed  Google Scholar 

  42. Damián JP, Vázquez Alberdi L, Canclini L, Rosso G, Bravo SO, Martínez M, Uriarte N, Ruiz P, Calero M, Di Tomaso MV, Kun A (2021) Central alteration in peripheral neuropathy of trembler-J Mice: hippocampal pmp22 expression and behavioral profile in anxiety tests. Biomolecules 11:601. https://doi.org/10.3390/biom11040601

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Ródenas-González F, Blanco-Gandía MC, Miñarro J, Rodríguez-Arias M (2022) Cognitive profile of male mice exposed to a ketogenic diet. Physiol Behav 254:113883. https://doi.org/10.1016/j.physbeh.2022.113883

    Article  CAS  PubMed  Google Scholar 

  44. Lach G, Schellekens H, Dinan TG, Cryan JF (2018) Anxiety, depression, and the microbiome: a role for gut peptides. Neurotherapeutics 15:36–59. https://doi.org/10.1007/s13311-017-0585-0

    Article  CAS  PubMed  Google Scholar 

  45. Limbana T, Khan F, Eskander N (2020) Gut microbiome and depression: how microbes affect the way we think. Cureus 12:e9966. https://doi.org/10.7759/cureus.9966

    Article  PubMed  PubMed Central  Google Scholar 

  46. Olson CA, Vuong HE, Yano JM, Liang QY, Nusbaum DJ, Hsiao EY (2018) The gut microbiota mediates the anti-seizure effects of the ketogenic diet. Cell 173:1728-1741.e13. https://doi.org/10.1016/j.cell.2018.04.027

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Ibrahim MK, Aboelsaad M, Tony F, Sayed M (2022) Garcinia cambogia extract alters anxiety, sociability, and dopamine turnover in male Swiss albino mice. SN Appl Sci 4:23. https://doi.org/10.1007/s42452-021-04902-z

    Article  CAS  Google Scholar 

  48. Semwal RB, Semwal DK, Vermaak I, Viljoen A (2015) A comprehensive scientific overview of Garcinia cambogia. Fitoterapia 102:134–148. https://doi.org/10.1016/j.fitote.2015.02.012

    Article  CAS  PubMed  Google Scholar 

  49. Corey R, Werner KT, Singer A, Moss A, Smith M, Noelting J, Rakela J (2016) Acute liver failure associated with Garcinia cambogia use. Ann Hepatol 15:123–126. https://doi.org/10.5604/16652681.1184287

    Article  PubMed  Google Scholar 

  50. Smith RJ, Bertilone C, Robertson AG (2016) Fulminant liver failure and transplantation after use of dietary supplements. Med J Aust 204:30–32. https://doi.org/10.5694/mja15.00816

    Article  PubMed  Google Scholar 

  51. Lobb A (2009) Hepatoxicity associated with weight-loss supplements: a case for better post-marketing surveillance. World J Gastroenterol 15:1786–1787. https://doi.org/10.3748/wjg.15.1786

    Article  PubMed  PubMed Central  Google Scholar 

  52. Ohia SE, Opere CA, LeDay AM, Bagchi M, Bagchi D, Stohs SJ (2002) Safety and mechanism of appetite suppression by a novel hydroxycitric acid extract (HCA-SX). Mol Cell Biochem 238:89–103. https://doi.org/10.1023/A:1019911205672

    Article  CAS  PubMed  Google Scholar 

  53. Lee KH, Lee BM (2007) Evaluation of the genotoxicity of (-)-hydroxycitric acid (HCA-SX) isolated from Garcinia cambogia. J Toxicol Environ Health A 70:388–392. https://doi.org/10.1080/15287390600882192

    Article  CAS  PubMed  Google Scholar 

  54. Louter-van de Haar J, Wielinga PY, Scheurink AJ, Nieuwenhuizen AG (2005) Comparison of the effects of three different (-)-hydroxycitric acid preparations on food intake in rats. Nutr Metab (Lond) 2:23. https://doi.org/10.1186/1743-7075-2-23

    Article  CAS  PubMed  Google Scholar 

  55. Kovacs EM, Westerterp-Plantenga MS, Saris WH (2001) The effects of 2-week ingestion of (–)-hydroxycitrate and (–)-hydroxycitrate combined with medium-chain triglycerides on satiety, fat oxidation, energy expenditure and body weight. Int J Obes Relat Metab Disord 25:1087–1094. https://doi.org/10.1038/sj.ijo.0801605

    Article  CAS  PubMed  Google Scholar 

  56. Sullivan C, Triscari J (1977) Metabolic regulation as a control for lipid disorders. I. Influence of (–)-hydroxycitrate on experimentally induced obesity in the rodent. Am J Clin Nutr 30:767–776. https://doi.org/10.1093/ajcn/30.5.767

    Article  CAS  PubMed  Google Scholar 

  57. Goudarzvand M, Afraei S, Yaslianifard S, Ghiasy S, Sadri G, Kalvandi M, Alinia T, Mohebbi A, Yazdani R, Azarian SK, Mirshafiey A, Azizi G (2016) Hydroxycitric acid ameliorates inflammation and oxidative stress in mouse models of multiple sclerosis. Neural Regen Res 11:1610–1616. https://doi.org/10.4103/1673-5374.193240

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Yin W, Signore AP, Iwai M, Cao G, Gao Y, Chen J (2008) Rapidly increased neuronal mitochondrial biogenesis after hypoxic-ischemic brain injury. Stroke 39:3057–3063. https://doi.org/10.1161/STROKEAHA.108.520114

    Article  PubMed  PubMed Central  Google Scholar 

  59. Xie Y, Li J, Fan G, Qi S, Li B (2014) Reperfusion promotes mitochondrial biogenesis following focal cerebral ischemia in rats. PloS one 9:e92443. https://doi.org/10.1371/journal.pone.0092443

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Chen H, Hu CJ, He YY, Yang DI, Xu J, Hsu CY (2001) Reduction and restoration of mitochondrial DNA content after focal cerebral ischemia/reperfusion. Stroke 32:2382–2387. https://doi.org/10.1161/hs1001.097099

    Article  CAS  PubMed  Google Scholar 

  61. Liu L, Zhang W, Wang L, Li Y, Tan B, Lu X, Deng Y, Zhang Y, Guo X, Mu J, Yu G (2014) Curcumin prevents cerebral ischemia reperfusion injury via increase of mitochondrial biogenesis. Neurochem Res 39:1322–1331. https://doi.org/10.1007/s11064-014-1315-1

    Article  CAS  PubMed  Google Scholar 

  62. Zhang Z, Yang D, Zhou B, Luan Y, Yao Q, Liu Y, Yang S, Jia J, Xu Y, Bie X, Wang Y, Li Z, Li A, Zheng H, He Y (2022) Decrease of MtDNA copy number affects mitochondrial function and involves in the pathological consequences of ischaemic stroke. J Cell Mol Med 26:4157–4168. https://doi.org/10.1111/jcmm.17262

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Scarpulla RC (2008) Transcriptional paradigms in mammalian mitochondrial biogenesis and function. Physiol Rev 88:611–638. https://doi.org/10.1152/physrev.00025.2007

    Article  CAS  PubMed  Google Scholar 

  64. Halling JF, Pilegaard H (2020) PGC-1α-mediated regulation of mitochondrial function and physiological implications. Appl Physiol Nutr Metab 45:927–936. https://doi.org/10.1139/apnm-2020-0005

    Article  CAS  PubMed  Google Scholar 

  65. Islam H, Hood DA, Gurd BJ (2020) Looking beyond PGC-1α: emerging regulators of exercise-induced skeletal muscle mitochondrial biogenesis and their activation by dietary compounds. Appl Physiol Nutr Metab 45:11–23. https://doi.org/10.1139/apnm-2019-0069

    Article  PubMed  Google Scholar 

  66. Gureev AP, Shaforostova EA, Popov VN (2019) Regulation of mitochondrial biogenesis as a way for active longevity: interaction between the Nrf2 and PGC-1α signaling pathways. Front Genet 10:435. https://doi.org/10.3389/fgene.2019.00435

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Sharma H, Singh A, Sharma C, Jain SK, Singh N (2005) Mutations in the mitochondrial DNA D-loop region are frequent in cervical cancer. Cancer Cell Int 5:34. https://doi.org/10.1186/1475-2867-5-34

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Cowell W, Brunst K, Colicino E, Zhang L, Zhang X, Bloomquist TR, Baccarelli AA, Wright RJ (2021) Placental mitochondrial DNA mutational load and perinatal outcomes: findings from a multi-ethnic pregnancy cohort. Mitochondrion 59:267–275. https://doi.org/10.1016/j.mito.2021.06.006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Ohtaki H, Takeda T, Dohi K, Yofu S, Nakamachi T, Satoh K, Hiraizumi Y, Miyaoka H, Matsunaga M, Shioda S (2007) Increased mitochondrial DNA oxidative damage after transient middle cerebral artery occlusion in mice. Neurosci Res 58:349–355. https://doi.org/10.1016/j.neures.2007.04.005

    Article  CAS  PubMed  Google Scholar 

  70. Milder JB, Liang LP, Patel M (2010) Acute oxidative stress and systemic Nrf2 activation by the ketogenic diet. Neurobiol Dis 40:238–244. https://doi.org/10.1016/j.nbd.2010.05.030

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Pinto A, Bonucci A, Maggi E, Corsi M, Businaro R (2018) Anti-oxidant and anti-inflammatory activity of ketogenic diet: new perspectives for neuroprotection in Alzheimer’s disease. Antioxidants (Basel) 7:63. https://doi.org/10.3390/antiox7050063

    Article  CAS  PubMed  Google Scholar 

  72. Piantadosi CA, Carraway MS, Babiker A, Suliman HB (2008) Heme oxygenase-1 regulates cardiac mitochondrial biogenesis via Nrf2-mediated transcriptional control of nuclear respiratory factor-1. Circ Res 103:1232–1240. https://doi.org/10.1161/01.RES.0000338597.71702.ad

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Jain A, Lamark T, Sjøttem E, Larsen KB, Awuh JA, Øvervatn A, McMahon M, Hayes JD, Johansen T (2010) p62/SQSTM1 is a target gene for transcription factor NRF2 and creates a positive feedback loop by inducing antioxidant response element-driven gene transcription. J Biol Chem 285:22576–22591. https://doi.org/10.1074/jbc.M110.118976

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Han JH, Park MH, Myung CS (2021) Garcinia cambogia ameliorates non-alcoholic fatty liver disease by inhibiting oxidative stress-mediated steatosis and apoptosis through NRF2-ARE activation. Antioxidants (Basel) 10:1226. https://doi.org/10.3390/antiox10081226

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank Dr. Nadezda Andrianova for useful comments and valuable discussions.

Funding

The work was supported by the Russian Science Foundation (grant #21–75-30009).

Author information

Authors and Affiliations

Authors

Contributions

A. P. G., D. N. S, V. N. P., and E. Y. P contributed to the design of experiments. D. N. S., I. S. S., E. P. K., E. V. C., D. E. V., N. A. S., D. V. P., I. Y. B., and Y. D. S. performed the experiments. A. P. G. and D. N. S. wrote the manuscript.

Corresponding author

Correspondence to Egor Y. Plotnikov.

Ethics declarations

Ethics approval

All procedures with animals, such as maintenance, all experimental techniques, and sacrifice, were performed by the rules set by Voronezh State University Ethical Committee on Biomedical Research (Section of Animal Care and Use, protocol 42–03 dated April 2, 2019) in accordance with the requirements of Directive 2010/63/EU of the European Parliament and of the Council of the European Union on the protection of animals used for scientific purposes.

Consent to Participate

Not applicable.

Consent for Publication

Not applicable.

Competing Interests

The authors declare no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Vasily N. Popov died before publication of this work was completed.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (XLSX 144 KB)

Supplementary file2 (PDF 321 KB)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Gureev, A.P., Silachev, D.N., Sadovnikova, I.S. et al. The Ketogenic Diet but not Hydroxycitric Acid Keeps Brain Mitochondria Quality Control and mtDNA Integrity Under Focal Stroke. Mol Neurobiol 60, 4288–4303 (2023). https://doi.org/10.1007/s12035-023-03325-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12035-023-03325-8

Keywords

Navigation