Skip to main content
Log in

Interval aerobic training improves bioenergetics state and mitochondrial dynamics of different brain regions in restraint stressed rats

  • Original Article
  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

Evidence has validated the prophylactic effects of exercising on different aspects of health. On the opposite side, immobilization may lead to various destructive effects causing neurodegeneration. Here, we investigated the association between exercising and mitochondrial quality for preventing the destructive effects of restraint stress in different rat brain regions. Twenty-four male Wistar rats, were randomized into four groups (n = 6), exercise, stress, exercise + stress, and control. The exercise procedure consisted of running on a rodent treadmill for 8 weeks, and rats in the stress group were immobilized for 6 h. Rats were then euthanized by decapitation and tricarboxylic acid (TCA) cycle enzyme activity, antioxidant levels, and mitochondrial biogenesis factors were assessed in the frontal, hippocampus, parietal and temporal regions using spectrophotometer and western blot technique. Based on our results, increased activity of TCA cycle enzymes in the exercised and exercise-stressed groups was detected, except for malate dehydrogenase which was decreased in exercise-stressed group, and fumarase that did not change. Furthermore, the level of antioxidant agents (superoxide dismutase and reduced glutathione), mitochondrial biogenesis factors (peroxisome proliferator-activated receptor gamma coactivator 1-alpha and mitochondrial transcription factor A), and dynamics markers (Mitofusin 2, dynamic related protein 1, PTEN induced putative kinase-1, and parkin) increased in both mentioned groups. Interestingly our results also revealed that the majority of the mitochondrial factors increased in the frontal and parietal lobes, which may be in relation with the location of motor and sensory areas. Exercise can be used as a prophylactic approach against bioenergetics and mitochondrial dysfunction.

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.

Scheme 1
Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Data availability

The data that support the findings of this study are available from the corresponding author, FF, if required.

References

  1. Sugama S, Sekiyama K, Kodama T et al (2016) Chronic restraint stress triggers dopaminergic and noradrenergic neurodegeneration: possible role of chronic stress in the onset of Parkinson’s disease. Brain Behav Immun 51:39–46

    Article  CAS  Google Scholar 

  2. Sántha P, Veszelka S, Hoyk Z et al (2016) Restraint stress-induced morphological changes at the blood-brain barrier in adult rats. Front Mol Neurosci 8:88

    Article  Google Scholar 

  3. Huang R-R, Hu W, Yin Y-Y et al (2015) Chronic restraint stress promotes learning and memory impairment due to enhanced neuronal endoplasmic reticulum stress in the frontal cortex and hippocampus in male mice. Int J Mol Med 35:553–559

    Article  CAS  Google Scholar 

  4. Fontella FU, Vendite DA, Tabajara AS et al (2004) Repeated restraint stress alters hippocampal glutamate uptake and release in the rat. Neurochem Res 29:1703–1709

    Article  CAS  Google Scholar 

  5. Madrigal JLM, Moro MA, Lizasoain I et al (2003) Induction of cyclooxygenase-2 accounts for restraint stress-induced oxidative status in rat brain. Neuropsychopharmacology 28:1579–1588

    Article  CAS  Google Scholar 

  6. Madrigal JLM, Olivenza R, Moro MA et al (2001) Glutathione depletion, lipid peroxidation and mitochondrial dysfunction are induced by chronic stress in rat brain. Neuropsychopharmacology 24:420–429

    Article  CAS  Google Scholar 

  7. Bowman RE, Ferguson D, Luine VN (2002) effects of chronic restraint stress and estradiol on open field activity, spatial memory, and monoaminergic neurotransmitters in ovariectomized. Neuroscience 113:401–410

    Article  CAS  Google Scholar 

  8. Maccari S, Morley-fletcher S (2007) Effects of prenatal restraint stress on the hypothalamus – pituitary – adrenal axis and related behavioural and neurobiological alterations. Psychoneuroendocrinology. https://doi.org/10.1016/j.psyneuen.2007.06.005

    Article  PubMed  Google Scholar 

  9. Şahin E, Gümüşlü S (2007) Immobilization stress in rat tissues: alterations in protein oxidation, lipid peroxidation and antioxidant defense system. Comp Biochem Physiol Part C Toxicol Pharmacol 144:342–347

    Article  Google Scholar 

  10. Bhat AH, Dar KB, Anees S et al (2015) Oxidative stress, mitochondrial dysfunction and neurodegenerative diseases; a mechanistic insight. Biomed Pharmacother 74:101–110

    Article  CAS  Google Scholar 

  11. Granata C, Jamnick NA, Bishop DJ (2018) Principles of exercise prescription, and how they influence exercise-induced changes of transcription factors and other regulators of mitochondrial biogenesis. Sport Med 1:1–19

    Google Scholar 

  12. Perry CG, Hawley JA (2017) Molecular basis of exercise-induced skeletal muscle mitochondrial biogenesis: historical advances, current knowledge, and future challenges. Cold Spring Harb Perspect Biol 8(9):a029686

    Article  Google Scholar 

  13. Ding Q, Vaynman S, Souda P et al (2006) Exercise affects energy metabolism and neural plasticity-related proteins in the hippocampus as revealed by proteomic analysis. Eur J Neurosci 24:1265–1276

    Article  Google Scholar 

  14. Gerecke KM, Kolobova A, Allen S, Fawer JL (2013) Exercise protects against chronic restraint stress-induced oxidative stress in the cortex and hippocampus. Brain Res 1509:66–78

    Article  CAS  Google Scholar 

  15. Naito H, Powers SK, Demirel HA, Aoki J (2001) Exercise training increases heat shock protein in skeletal muscles of old rats. Med Sci Sports Exerc 33:729–734

    Article  CAS  Google Scholar 

  16. Khalaj L, Chavoshi Nejad S, Mohammadi M et al (2013) Assessing competence of broccoli consumption on inflammatory and antioxidant pathways in restraint-induced models: estimation in rat hippocampus and prefrontal cortex. Biomed Res Int. https://doi.org/10.1155/2013/590379

    Article  PubMed  PubMed Central  Google Scholar 

  17. Feng P, Guan Z, Yang X, Fang J (2003) Impairments of ERK signal transduction in the brain in a rat model of depression induced by neonatal exposure of clomipramine. Brain Res 991:195–205. https://doi.org/10.1016/j.brainres.2003.08.018

    Article  CAS  PubMed  Google Scholar 

  18. Clarke DD, Nicklas WJ, Berl S (1970) Tricarboxylic acid-cycle metabolism in brain. Effect of fluoroacetate and fluorocitrate on the labelling of glutamate, aspartate, glutamine and gamma-aminobutyrate. Biochem J 120:345–351. https://doi.org/10.1042/bj1200345

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254

    Article  CAS  Google Scholar 

  20. Powell CS, Jackson RM (2003) Mitochondrial complex I, aconitase, and succinate dehydrogenase during hypoxia-reoxygenation: modulation of enzyme activities by MnSOD. Am J Physiol Lung Cell Mol Physiol 285:L189–L198. https://doi.org/10.1152/ajplung.00253.2002

    Article  CAS  PubMed  Google Scholar 

  21. Vásquez-Vivar J, Kalyanaraman B, Kennedy MC (2000) Mitochondrial aconitase is a source of hydroxyl radical an electron spin resonance investigation. J Biol Chem 275:14064–14069

    Article  Google Scholar 

  22. Gibson GE, Sheu KF, Blass JP et al (1988) Reduced activities of thiamine-dependent enzymes in the brains and peripheral tissues of patients with Alzheimer’s disease. Arch Neurol 45:836–840

    Article  CAS  Google Scholar 

  23. Racker E (1950) Spectrophotometric measurements of the enzymatic formation of fumaric and cis-aconitic acids. BBA Biochim Biophys Acta 4:211–214. https://doi.org/10.1016/0006-3002(50)90026-6

    Article  CAS  PubMed  Google Scholar 

  24. Wang Q, Yu L, Yu C-A (2010) Cross-talk between mitochondrial malate dehydrogenase and the cytochrome bc1 complex. J Biol Chem 285:10408–10414

    Article  CAS  Google Scholar 

  25. Kakkar P, Das B, Viswanathan PN (1984) A modified spectrophotometric assay of superoxide dismutase. Indian J Biochem Biophys 21:130–132. https://doi.org/10.1097/YCO.0b013e3280117733

    Article  CAS  PubMed  Google Scholar 

  26. Ellman GL (1959) Tissue Su ~ yd ~ l groups. Am J Anal Chem 1:70–77

    Google Scholar 

  27. Fernie AR, Carrari F, Sweetlove LJ (2004) Respiratory metabolism: glycolysis, the TCA cycle and mitochondrial electron transport. Curr Opin Plant Biol 7:254–261. https://doi.org/10.1016/j.pbi.2004.03.007

    Article  CAS  PubMed  Google Scholar 

  28. Ma YS, Wu SB, Lee WY et al (2009) Response to the increase of oxidative stress and mutation of mitochondrial DNA in aging. Biochim Biophys Acta - Gen Subj 1790:1021–1029. https://doi.org/10.1016/j.bbagen.2009.04.012

    Article  CAS  Google Scholar 

  29. Lubitz W, Ogata H (2013) Hydrogenases, structure and function. Encycl Biol Chem Second Ed. https://doi.org/10.1016/B978-0-12-378630-2.00205-X

    Article  Google Scholar 

  30. Lee H, Yoon Y (2012) Mitochondrial dynamics: mechanisms and pathologies. eLS, American Cancer Society. https://doi.org/10.1002/9780470015902.a0021867

  31. Liu P, Lin H, Xu Y et al (2018) Frataxin-mediated PINK1-Parkin-dependent mitophagy in hepatic steatosis: the protective effects of quercetin. Mol Nutr Food Res. https://doi.org/10.1002/mnfr.201800164

    Article  PubMed  PubMed Central  Google Scholar 

  32. Rakovic A, Grünewald A, Kottwitz J et al (2011) Mutations in PINK1 and Parkin impair ubiquitination of Mitofusins in human fibroblasts. PLoS ONE 6:e16746

    Article  CAS  Google Scholar 

  33. Holloszy JO, Oscai LB, Don IJ, Mole PA (1970) Mitochondrial citric acid cycle and related enzymes: adaptive response to exercise. Biochem Biophys Res Commun 40:1368–1373

    Article  CAS  Google Scholar 

  34. Foster PP, Rosenblatt KP, Kuljiš RO (2011) Exercise-induced cognitive plasticity, implications for mild cognitive impairment and Alzheimer’s disease. Front Neurol. https://doi.org/10.3389/fneur.2011.00028

    Article  PubMed  PubMed Central  Google Scholar 

  35. LaNoue KF, Bryla J, Williamson JR (1972) Feedback interactions in the control of citric acid cycle activity in rat heart mitochondria. J Biol Chem 247:667–679

    Article  CAS  Google Scholar 

  36. Minoshima S, Giordani B, Berent S et al (1997) Metabolic reduction in the posterior cingulate cortex in very early Alzheimer’s disease. Ann Neurol Off J Am Neurol Assoc Child Neurol Soc 42:85–94

    CAS  Google Scholar 

  37. Mosconi L, Tsui WH, Herholz K et al (2008) Multicenter standardized 18F-FDG PET diagnosis of mild cognitive impairment, Alzheimer’s disease, and other dementias. J Nucl Med Off Publ Soc Nucl Med 49:390

    Google Scholar 

  38. Sorbi S, Bird ED, Blass JP (1983) Decreased pyruvate dehydrogenase complex activity in Huntington and Alzheimer brain. Ann Neurol 13:72–78

    Article  CAS  Google Scholar 

  39. Gibson GE, Shi Q (2010) A mitocentric view of Alzheimer’s disease suggests multi-faceted treatments. J Alzheimer’s Dis. https://doi.org/10.3233/JAD-2010-100336

    Article  Google Scholar 

  40. Bhattacharya SB, Datta AG (1993) Is brain a gluconeogenic organ? Mol Cell Biochem 125:51–57

    Article  CAS  Google Scholar 

  41. Hung G-C, Brown CR, Wolfe AB et al (2004) Degradation of the gluconeogenic enzymes fructose-1, 6-bisphosphatase and malate dehydrogenase is mediated by distinct proteolytic pathways and signaling events. J Biol Chem 279:49138–49150

    Article  CAS  Google Scholar 

  42. Yip J, Geng X, Shen J, Ding Y (2017) Cerebral gluconeogenesis and diseases. Front Pharmacol 7:521. https://doi.org/10.3389/fphar.2016.00521

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Yuan X, Rietzschel N, Kwon H et al (2016) Regulation of intracellular heme trafficking revealed by subcellular reporters. Proc Natl Acad Sci U S A 113:E5144–E5152. https://doi.org/10.1073/pnas.1609865113

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Benarroch EE (2009) Brain iron homeostasis and neurodegenerative disease. Neurology 72:1436–1440

    Article  Google Scholar 

  45. Freitas HR, Ferraz G, Ferreira GC et al (2016) Glutathione-induced calcium shifts in chick retinal glial cells. PLoS ONE 11:1–20. https://doi.org/10.1371/journal.pone.0153677

    Article  CAS  Google Scholar 

  46. Bugg JM, Head D (2011) Exercise moderates age-related atrophy of the medial temporal lobe. Neurobiol Aging 32:506–514

    Article  Google Scholar 

  47. Gleyzer N, Vercauteren K, Scarpulla RC (2005) Control of mitochondrial transcription specificity factors (TFB1M and TFB2M) by nuclear respiratory factors (NRF-1 and NRF-2) and PGC-1 family coactivators. Mol Cell Biol 25:1354–1366

    Article  CAS  Google Scholar 

  48. Kim JH, Shin HD, Park BL et al (2005) Peroxisome proliferator-activated receptor gamma coactivator 1 alpha promoter polymorphisms are associated with early-onset type 2 diabetes mellitus in the Korean population. Diabetologia 48:1323–1330. https://doi.org/10.1007/s00125-005-1793-4

    Article  CAS  PubMed  Google Scholar 

  49. Robinson MM, Lowe VJ, Nair KS (2018) Increased brain glucose uptake after 12 weeks of aerobic high-intensity interval training in young and older adults. J Clin Endocrinol Metab 103:221–227. https://doi.org/10.1210/jc.2017-01571

    Article  PubMed  Google Scholar 

  50. Twig G, Shirihai OS (2010) The interplay between mitochondrial dynamics and mitophagy. Antioxid Redox Signal 14:1939–1951. https://doi.org/10.1089/ars.2010.3779

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by The Research grant of Shahid Beheshti University of Medical Sciences (No.11844‐2).

Funding

This work was supported by The Research grant of Shahid Beheshti University of Medical Sciences (No.11844‐2).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Forough Foolad.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethics approval

The experiments were performed after approval by the Ethics Committee of the institution (Ethics code: IR.SBMU.PHNS.REC.1396.34).

Additional information

Publisher's Note

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

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Khodagholi, F., Zareh Shahamati, S., Maleki Chamgordani, M. et al. Interval aerobic training improves bioenergetics state and mitochondrial dynamics of different brain regions in restraint stressed rats. Mol Biol Rep 48, 2071–2082 (2021). https://doi.org/10.1007/s11033-021-06177-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-021-06177-4

Keywords

Navigation