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Effect of coenzyme Q10 supplementation on diabetes induced memory deficits in rats

  • Ghazaleh Omidi
  • Seyed Asaad Karimi
  • Arezoo Rezvani-Kamran
  • Amirreza Monsef
  • Siamak Shahidi
  • Alireza KomakiEmail author
Original Article
  • 23 Downloads

Abstract

The main objective of current work was to determine the effects of low and high dose supplementation with coenzyme Q10 (CoQ10) on spatial learning and memory in rats with streptozotocin (STZ)-induced diabetes. Male Wistar rats (weighing 220 ± 10) were randomly divided into six groups: (i) Control (Con, n = 8); (ii) Control+ Low dose of CoQ10 (100 mg/kg) (CLD, n = 10); (iii) Control+ high dose of CoQ10 (600 mg/kg) (CHD, n = 10); (iv) Diabetic (D, n = 10); (v) Diabetic + Low dose of CoQ10 (100 mg/kg) (DLD, n = 10); (vi) Diabetic + high dose of CoQ10 (600 mg/kg) (DHD, n = 10). Diabetes was induced by a single intraperitoneal injection of 50 mg/kg STZ. CoQ10 was administered intragastrically by gavage once a day for 90 days. After 90 days, Morris water maze (MWM) task was used to evaluate the spatial learning and memory in rats. Diabetic animals showed a slower rate of acquisition with respect to the control animals [F (1, 51) = 92.81, P < 0.0001, two-way ANOVA]. High dose (but no low dose) supplementation with CoQ10 could attenuate deteriorative effect of diabetes on memory acquisition. Diabetic animals which received CoQ10 (600 mg/kg) show a considerable decrease in escape latency and traveled distance compared to diabetic animals (p < 0.05, two-way ANOVA,). The present study has shown that low dose supplementation with CoQ10 in diabetic rats failed to improve deficits in cognitive function but high dose supplementation with CoQ10 reversed diabetes-related declines in spatial learning.

Keywords

Diabetes mellitus Coenzyme Q10 (CoQ10) Learning and memory Wistar rats 

Notes

Acknowledgements

The authors would like to express their gratitude to the staff of the Neurophysiology Research Center for helping us to carry out this project. This research was supported by a grant (grant number: IR.UMSHA.REC.1394.360) of the Neurophysiology Research Center, Hamadan University of Medical Sciences, Hamadan, Iran.

Compliance with ethical standards

Conflict of interest statement

We confirm that the authors do not have any conflict of interest with this publication.

References

  1. Ahmad M, Saleem S, Ahmad AS, Yousuf S, Ansari MA, Khan MB, Ishrat T, Chaturvedi RK, Agrawal AK, Islam F (2005) Ginkgo biloba affords dose-dependent protection against 6-hydroxydopamine-induced parkinsonism in rats: neurobehavioural, neurochemical and immunohistochemical evidences. J Neurochem 93:94–104CrossRefGoogle Scholar
  2. Aksenov M, Aksenova M, Butterfield D, Geddes J, Markesbery W (2001) Protein oxidation in the brain in Alzheimer's disease. Neuroscience 103:373–383CrossRefGoogle Scholar
  3. Arvanitakis Z, Wilson RS, Li Y, Aggarwal NT, Bennett DA (2006) Diabetes and function in different cognitive systems in older individuals without dementia. Diabetes Care 29:560–565CrossRefGoogle Scholar
  4. Asadbegi M, Yaghmaei P, Salehi I, Komaki A, Ebrahim-Habibi A (2017) Investigation of thymol effect on learning and memory impairment induced by intrahippocampal injection of amyloid beta peptide in high fat diet-fed rats. Metab Brain Dis 32:827–839CrossRefGoogle Scholar
  5. Association AD (2016) 2. Classification and diagnosis of diabetes. Diabetes Care 39:S13–S22CrossRefGoogle Scholar
  6. Bashan N, Kovsan J, Kachko I, Ovadia H, Rudich A (2009) Positive and negative regulation of insulin signaling by reactive oxygen and nitrogen species. Physiol Rev 89:27–71CrossRefGoogle Scholar
  7. Baydas G, Nedzvetskii VS, Nerush PA, Kirichenko SV, Yoldas T (2003) Altered expression of NCAM in hippocampus and cortex may underlie memory and learning deficits in rats with streptozotocin-induced diabetes mellitus. Life Sci 73:1907–1916CrossRefGoogle Scholar
  8. Beal MF (2004a) Mitochondrial dysfunction and oxidative damage in Alzheimer's and Parkinson's diseases and coenzyme Q 10 as a potential treatment. J Bioenerg Biomembr 36:381–386CrossRefGoogle Scholar
  9. Beal MF (2004b) Therapeutic effects of coenzyme Q10 in neurodegenerative diseases. In: Methods in enzymology. Elsevier, pp 473–487Google Scholar
  10. Beal MF, Henshaw DR, Jenkins BG, Rosen BR, Schulz JB (1994) Coenzyme Q10 and nicotinamide block striatal lesions produced by the mitochondrial toxin malonate. Ann Neurol 36:882–888CrossRefGoogle Scholar
  11. Berr C, Balansard B, Arnaud J, Roussel AM, Alpérovitch A, Group ES (2000) Cognitive decline is associated with systemic oxidative stress: the EVA study. J Am Geriatr Soc 48:1285–1291CrossRefGoogle Scholar
  12. Bhagavan HN, Chopra RK (2006) Coenzyme Q10: absorption, tissue uptake, metabolism and pharmacokinetics. Free Radic Res 40:445–453CrossRefGoogle Scholar
  13. Brands AM, Biessels GJ, De Haan EH, Kappelle LJ, Kessels RP (2005) The effects of type 1 diabetes on cognitive performance: a meta-analysis. Diabetes Care 28:726–735CrossRefGoogle Scholar
  14. Brismar T, Maurex L, Cooray G, Juntti-Berggren L, Lindström P, Ekberg K, Adner N, Andersson S (2007) Predictors of cognitive impairment in type 1 diabetes. Psychoneuroendocrinology 32:1041–1051CrossRefGoogle Scholar
  15. Care IoLARCo, Animals UoL, Resources NIoHDoR (1985) Guide for the care and use of laboratory animals: National AcademiesGoogle Scholar
  16. Crane FL (2001) Biochemical functions of coenzyme Q10. J Am Coll Nutr 20:591–598CrossRefGoogle Scholar
  17. Cummings JL (2000) The role of cholinergic agents in the management of behavioural disturbances in Alzheimer's disease. Int J Neuropsychopharmacol 3:S21–S29CrossRefGoogle Scholar
  18. El-ghoroury EA, Raslan HM, Badawy EA, El-Saaid GS, Agybi MH, Siam I, Salem SI (2009) Malondialdehyde and coenzyme Q10 in platelets and serum in type 2 diabetes mellitus: correlation with glycemic control. Blood Coagul Fibrinolysis 20:248–251CrossRefGoogle Scholar
  19. Ernster L, Dallner G (1995) Biochemical, physiological and medical aspects of ubiquinone function. Biochim Biophys Acta (BBA) - Mol Basis Dis 1271:195–204CrossRefGoogle Scholar
  20. Fukui K, Onodera K, Shinkai T, Suzuki S, Urano S (2001) Impairment of learning and memory in rats caused by oxidative stress and aging, and changes in antioxidative defense systems. Ann N Y Acad Sci 928:168–175CrossRefGoogle Scholar
  21. Furman BL (2015) Streptozotocin-induced diabetic models in mice and rats. Curr Protoc Pharmacol 70:5.47.1–20Google Scholar
  22. Groneberg DA, Kindermann B, Althammer M, Klapper M, Vormann J, Littarru GP, Döring F (2005) Coenzyme Q10 affects expression of genes involved in cell signalling, metabolism and transport in human CaCo-2 cells. Int J Biochem Cell Biol 37:1208–1218CrossRefGoogle Scholar
  23. Hajisoltani R, Karimi SA, Rahdar M, Davoudi S, Borjkhani M, Hosseinmardi N, Behzadi G, Janahmadi M (2019) Hyperexcitability of hippocampal CA1 pyramidal neurons in male offspring of a rat model of autism spectrum disorder (ASD) induced by prenatal exposure to valproic acid: a possible involvement of Ih channel current. Brain Res 1708:188–199CrossRefGoogle Scholar
  24. Hidaka T, Fujii K, Funahashi I, Fukutomi N, Hosoe K (2008) Safety assessment of coenzyme Q10 (CoQ10). Biofactors 32:199–208CrossRefGoogle Scholar
  25. Hosoe K, Kitano M, Kishida H, Kubo H, Fujii K, Kitahara M (2007) Study on safety and bioavailability of ubiquinol (Kaneka QH™) after single and 4-week multiple oral administration to healthy volunteers. Regul Toxicol Pharmacol 47:19–28CrossRefGoogle Scholar
  26. Ishrat T, Khan MB, Hoda MN, Yousuf S, Ahmad M, Ansari MA, Ahmad AS, Islam F (2006) Coenzyme Q10 modulates cognitive impairment against intracerebroventricular injection of streptozotocin in rats. Behav Brain Res 171:9–16CrossRefGoogle Scholar
  27. Karimi SA, Hosseinmardi N, Janahmadi M, Sayyah M, Hajisoltani R (2017) The protective effect of hydrogen sulfide (H2S) on traumatic brain injury (TBI) induced memory deficits in rats. Brain Res Bull 134:177–182CrossRefGoogle Scholar
  28. Karimi SA, Salehi I, Shykhi T, Zare S, Komaki A (2019) Effects of exposure to extremely low-frequency electromagnetic fields on spatial and passive avoidance learning and memory, anxiety-like behavior and oxidative stress in male rats. Behav Brain Res 359:630–638CrossRefGoogle Scholar
  29. Kucukatay V, Ağar A, Gumuslu S, Yargiçoğlu P (2007) Effect of sulfur dioxide on active and passive avoidance in experimental diabetes mellitus: relation to oxidant stress and antioxidant enzymes. Int J Neurosci 117:1091–1107CrossRefGoogle Scholar
  30. Kwong LK, Kamzalov S, Rebrin I, Bayne A-CV, Jana CK, Morris P, Forster MJ, Sohal RS (2002) Effects of coenzyme Q10 administration on its tissue concentrations, mitochondrial oxidant generation, and oxidative stress in the rat. Free Radic Biol Med 33:627–638CrossRefGoogle Scholar
  31. Lass A, Sohal RS (1998) Electron transport-linked ubiquinone-dependent recycling of α-tocopherol inhibits autooxidation of mitochondrial membranes. Arch Biochem Biophys 352:229–236CrossRefGoogle Scholar
  32. Lenaz G, Bovina C, Formiggini G, Parenti GC (1999) Mitochondria, oxidative stress, and antioxidant defences. Acta Biochim Pol 46:1–21Google Scholar
  33. Littarru GP, Lambrechts P (2011) Coenzyme Q 10: multiple benefits in one ingredient. Oléagineux, Corps gras, Lipides 18:76–82CrossRefGoogle Scholar
  34. Matthews RT, Yang L, Browne S, Baik M, Beal MF (1998) Coenzyme Q10 administration increases brain mitochondrial concentrations and exerts neuroprotective effects. Proc Natl Acad Sci 95:8892–8897CrossRefGoogle Scholar
  35. McDonald SR, Sohal RS, Forster MJ (2005) Concurrent administration of coenzyme Q10 and α-tocopherol improves learning in aged mice. Free Radic Biol Med 38:729–736CrossRefGoogle Scholar
  36. Moradkhani S, Salehi I, Abdolmaleki S, Komaki A (2015) Effect of Calendula officinalis hydroalcoholic extract on passive avoidance learning and memory in streptozotocin-induced diabetic rats. Anc Sci Life 34:157Google Scholar
  37. Niedzielska E, Smaga I, Gawlik M, Moniczewski A, Stankowicz P, Pera J, Filip M (2016) Oxidative stress in neurodegenerative diseases. Mol Neurobiol 53:4094–4125CrossRefGoogle Scholar
  38. Quinzii CM, López LC, Gilkerson RW, Dorado B, Coku J, Naini AB, Lagier-Tourenne C, Schuelke M, Salviati L, Carrozzo R (2010) Reactive oxygen species, oxidative stress, and cell death correlate with level of CoQ10 deficiency. FASEB J 24:3733–3743CrossRefGoogle Scholar
  39. Rauchova H, Drahota Z, Lenaz G (1995) Function of coenzyme Q in the cell: some biochemical and physiological properties. Physiol Res 44:209–209Google Scholar
  40. Rezvani-Kamran A, Salehi I, Shahidi S, Zarei M, Moradkhani S, Komaki A (2017) Effects of the hydroalcoholic extract of Rosa damascena on learning and memory in male rats consuming a high-fat diet. Pharm Biol 55:2065–2073CrossRefGoogle Scholar
  41. Ristow M (2004) Neurodegenerative disorders associated with diabetes mellitus. J Mol Med 82:510–529CrossRefGoogle Scholar
  42. Saedi E, Gheini MR, Faiz F, Arami MA (2016) Diabetes mellitus and cognitive impairments. World J Diabetes 7:412–422CrossRefGoogle Scholar
  43. Sandhir R, Sethi N, Aggarwal A, Khera A (2014) Coenzyme Q10 treatment ameliorates cognitive deficits by modulating mitochondrial functions in surgically induced menopause. Neurochem Int 74:16–23CrossRefGoogle Scholar
  44. Shen Q, Pierce J (2015) Supplementation of coenzyme Q10 among patients with type 2 diabetes mellitus. In: Healthcare: Multidisciplinary Digital Publishing Institute. p 296–309Google Scholar
  45. Shetty RA, Forster MJ, Sumien N (2013) Coenzyme Q 10 supplementation reverses age-related impairments in spatial learning and lowers protein oxidation. Age 35:1821–1834CrossRefGoogle Scholar
  46. Somayajulu M, McCarthy S, Hung M, Sikorska M, Borowy-Borowski H, Pandey S (2005) Role of mitochondria in neuronal cell death induced by oxidative stress; neuroprotection by coenzyme Q10. Neurobiol Dis 18:618–627CrossRefGoogle Scholar
  47. Sumien N, Heinrich KR, Shetty RA, Sohal RS, Forster MJ (2009) Prolonged intake of coenzyme Q10 impairs cognitive functions in mice. J Nutr 139:1926–1932CrossRefGoogle Scholar
  48. Tiwari V, Kuhad A, Bishnoi M, Chopra K (2009) Chronic treatment with tocotrienol, an isoform of vitamin E, prevents intracerebroventricular streptozotocin-induced cognitive impairment and oxidative-nitrosative stress in rats. Pharmacol Biochem Behav 93:183–189CrossRefGoogle Scholar
  49. Turunen M, Olsson J, Dallner G (2004) Metabolism and function of coenzyme Q. Biochim. Biophys Acta Biomembr 1660:171–199CrossRefGoogle Scholar
  50. Vijayakumar T, Sirisha G, Farzana Begam M, Dhanaraju M (2012) Mechanism linking cognitive impairment and diabetes mellitus. European Journal of Applied Sciences 4:1–5Google Scholar
  51. Volpe CMO, Villar-Delfino PH, dos Anjos PMF, Nogueira-Machado JA (2018) Cellular death, reactive oxygen species (ROS) and diabetic complications. Cell Death Dis 9:119CrossRefGoogle Scholar
  52. Zahedi H, Eghtesadi S, Seifirad S, Rezaee N, Shidfar F, Heydari I, Golestan B, Jazayeri S (2014) Effects of CoQ10 supplementation on lipid profiles and glycemic control in patients with type 2 diabetes: a randomized, double blind, placebo-controlled trial. J Diabetes Metab 13:81Google Scholar
  53. Zarrinkalam E, Heidarianpour A, Salehi I, Ranjbar K, Komaki A (2016) Effects of endurance, resistance, and concurrent exercise on learning and memory after morphine withdrawal in rats. Life Sci 157:19–24CrossRefGoogle Scholar
  54. Zarrinkalam E, Ranjbar K, Salehi I, Kheiripour N, Komaki A (2018) Resistance training and hawthorn extract ameliorate cognitive deficits in streptozotocin-induced diabetic rats. Biomed Pharmacother 97:503–510CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Neurophysiology Research CenterHamadan University of Medical SciencesHamadanIran
  2. 2.Department of Neuroscience, School of Advanced Technologies in MedicineHamadan University of Medical SciencesHamadanIran
  3. 3.Department of Physiology, School of MedicineHamadan University of Medical SciencesHamadanIran

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