Skip to main content
Log in

Coenzyme Q10 reduces expression of apoptotic markers in adult rat nucleus accumbens dopaminergic neurons treated with methamphetamine

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

Abstract

Background

Abuse of addictive drugs such as methamphetamine (METH) has become a global problem, leading to many social, economic, and health disturbances, including neurological and cognitive disorders. Neuronal damage is reported in chronic METH abusers. The neuroprotective role of CoQ10 has been shown in many studies. In the present study, we aimed to assess the pre and post-efficacy of CoQ10 on the dopaminergic neurons of the Nucleus Accumbens (de Miranda et al. in Food Res Int 121:641–647, 2019) in the male adult rats treated with METH.

Methods

80 rats were randomly divided into eight groups (n = 10), including: negative control (intact), positive control (received 5 mg/kg/day METH/IP), three post-treatment groups (METH + 5, 10, 20 mg/kg CoQ10) and three pre-treatment groups (received 5, 10, 20 mg/kg CoQ10 as pre-treatment for 14 days before METH injection). The expression of Bax, Bcl-2, Bax/Bcl-2 ratio, P53, Caspase-3 and tyrosine hydroxylase in NAc studied using western blotting. Nissl staining was used to study the neuronal density of NAc.

Results

Our results showed that the different doses of CoQ10 in METH-treated animals significantly changed pro-apoptotic proteins’ expression in the benefit of neuronal survival of NAc (P < 0.05). Neuronal density in NAc were significantly lower in the METH group compared to the control and CoQ10 treated groups. Pre- and post-treatment with different doses of CoQ10 restored the neuronal damage in NAc.

Conclusions

CoQ10 could decrease the activation of pro-apoptotic proteins and reduce the neurodegenerative effects induced by METH. From a clinical point of view, it seems that certain antioxidants such as CoQ10 should receive more attention in clinical trial research. We believe that antioxidants could be the promising for drug abuse treatment in the future.

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

Similar content being viewed by others

References

  1. Peacock A, Leung J, Larney S, Colledge S, Hickman M, Rehm J et al (2018) Global statistics on alcohol, tobacco and illicit drug use: 2017 status report. Addiction 113(10):1905–1926

    Article  PubMed  Google Scholar 

  2. Potvin S, Pelletier J, Grot S, Hebert C, Barr AM, Lecomte T (2018) Cognitive deficits in individuals with methamphetamine use disorder: a meta-analysis. Addict Behav 80:154–160

    Article  PubMed  Google Scholar 

  3. Turowski P, Kenny B-A (2015) The blood-brain barrier and methamphetamine: open sesame? Front NeuroSci 9:156

    Article  PubMed  PubMed Central  Google Scholar 

  4. Thrash B, Karuppagounder SS, Uthayathas S, Suppiramaniam V, Dhanasekaran M (2010) Neurotoxic effects of methamphetamine. Neurochem Res 35(1):171–179

    Article  CAS  PubMed  Google Scholar 

  5. Rocha A, Kalivas PW (2010) Role of the prefrontal cortex and nucleus accumbens in reinstating methamphetamine seeking. Eur J Neurosci 31(5):903–909

    Article  PubMed  PubMed Central  Google Scholar 

  6. Moszczynska A, Callan SP (2017) Molecular, behavioral, and physiological consequences of methamphetamine neurotoxicity: implications for treatment. J Pharmacol Exp Ther 362(3):474–488

    Article  CAS  PubMed  Google Scholar 

  7. Moszczynska A, Yamamoto BK (2011) Methamphetamine oxidatively damages parkin and decreases the activity of 26S proteasome in vivo. J Neurochem 116(6):1005–1017

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Limanaqi F, Gambardella S, Biagioni F, Busceti CL, Fornai F (2018) Epigenetic effects induced by methamphetamine and methamphetamine-dependent oxidative stress. Oxidative Med Cell Longev. https://doi.org/10.1155/2018/4982453

    Article  Google Scholar 

  9. Frank MG, Adhikary S, Sobesky JL, Weber MD, Watkins LR, Maier SF (2016) The danger-associated molecular pattern HMGB1 mediates the neuroinflammatory effects of methamphetamine. Brain Behav Immun 51:99–108

    Article  CAS  PubMed  Google Scholar 

  10. Halpin LE, Collins SA, Yamamoto BK (2014) Neurotoxicity of methamphetamine and 3, 4-methylenedioxymethamphetamine. Life Sci 97(1):37–44

    Article  CAS  PubMed  Google Scholar 

  11. Chen C, Qincao L, Xu J, Du S, Huang E, Liu C et al (2016) Role of PUMA in methamphetamine-induced neuronal apoptosis. Toxicol Lett 240(1):149–160

    Article  CAS  PubMed  Google Scholar 

  12. Elyasi L, Eftekhar-Vaghefi SH, Esmaeili-Mahani S (2014) Morphine protects SH-SY5Y human neuroblastoma cells against 6-hydroxydopamine–induced cell damage: involvement of anti-oxidant, calcium blocking, and anti-apoptotic properties. Rejuven Res 17(3):255–263

    Article  CAS  Google Scholar 

  13. Nopparat C, Porter JE, Ebadi M, Govitrapong P (2010) The mechanism for the neuroprotective effect of melatonin against methamphetamine-induced autophagy. J Pineal Res 49(4):382–389

    Article  CAS  PubMed  Google Scholar 

  14. Bank G, Kagan D, Madhavi D (2011) Coenzyme Q10: clinical update and bioavailability. J Evid-Based Complement Altern Med 16(2):129–137

    Article  CAS  Google Scholar 

  15. Yang X, Zhang Y, Xu H, Luo X, Yu J, Liu J et al (2016) Neuroprotection of coenzyme Q10 in neurodegenerative diseases. Curr Top Med Chem 16(8):858–866

    Article  CAS  PubMed  Google Scholar 

  16. Thanh HN, Minh HPT, Duc LV, Thanh TB (2016) Protective effect of coenzyme Q10 on methamphetamine-induced neurotoxicity in the mouse brain. Trends Med Res 11(1):1–10

    Article  CAS  Google Scholar 

  17. Klongpanichapak S, Govitrapong P, Sharma SK, Ebadi M (2006) Attenuation of cocaine and methamphetamine neurotoxicity by coenzyme Q 10. Neurochem Res 31(3):303–311

    Article  CAS  PubMed  Google Scholar 

  18. Gholipour F, Shams J, Zahiroddin A (2017) Protective effect of coenzyme Q10 on methamphetamine-induced apoptosis in adult male rats. Nov Biomed 5(3):127–132

    CAS  Google Scholar 

  19. Jameie SB, Masoumipoor M, Janzadeh A, Nasirinezhad F, Kerdari M, Soleimani M (2014) Combined therapeutic effects of low power laser (980 nm) and CoQ10 on Neuropathic Pain in adult male rat. Med J Islam Repub Iran 28:58

    PubMed  PubMed Central  Google Scholar 

  20. Björklund A, Dunnett SB (2019) The amphetamine induced rotation test: a re-assessment of its use as a tool to monitor motor impairment and functional recovery in rodent models of Parkinson’s disease. J Parkinson’s Dis 9(1):17–29

    Article  Google Scholar 

  21. Thanos PK, Kim R, Delis F, Ananth M, Chachati G, Rocco MJ et al (2016) Chronic methamphetamine effects on brain structure and function in rats. PLoS One 11(6):e0155457

    Article  PubMed  PubMed Central  Google Scholar 

  22. Hori N, Kadota M, Watanabe M, Ito Y, Akaike N, Carpenter D (2010) Neurotoxic effects of methamphetamine on rat hippocampus pyramidal neurons. Cell Mol Neurobiol 30(6):849–856

    Article  CAS  PubMed  Google Scholar 

  23. Martin TA, Jayanthi S, McCoy MT, Brannock C, Ladenheim B, Garrett T et al (2012) Methamphetamine causes differential alterations in gene expression and patterns of histone acetylation/hypoacetylation in the rat nucleus accumbens. PLoS One 7(3):e34236

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Yu S, Zhu L, Shen Q, Bai X, Di X (2015) Recent advances in methamphetamine neurotoxicity mechanisms and its molecular pathophysiology. Behav Neurol. https://doi.org/10.1155/2015/103969

    Article  PubMed  PubMed Central  Google Scholar 

  25. Zhou F, Yang Y, Xing D (2011) Bcl-2 and Bcl‐xL play important roles in the crosstalk between autophagy and apoptosis. FEBS J 278(3):403–413

    Article  CAS  PubMed  Google Scholar 

  26. Huang W, Xie W-B, Qiao D, Qiu P, Huang E, Li B et al (2015) Caspase-11 plays an essential role in methamphetamine-induced dopaminergic neuron apoptosis. Toxicol Sci 145(1):68–79

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Parrish AB, Freel CD, Kornbluth S (2013) Cellular mechanisms controlling caspase activation and function. Cold Spring Harb Perspect Biol 5(6):a008672

    Article  PubMed  PubMed Central  Google Scholar 

  28. Reiner DJ, Yu S-J, Shen H, He Y, Bae E, Wang Y (2014) 9-Cis retinoic acid protects against methamphetamine-induced neurotoxicity in nigrostriatal dopamine neurons. Neurotox Res 25(3):248–261

    Article  CAS  PubMed  Google Scholar 

  29. Bentinger M, Tekle M, Dallner G (2010) Coenzyme Q–biosynthesis and functions. Biochem Biophys Res Commun 396(1):74–79

    Article  CAS  PubMed  Google Scholar 

  30. Badawy Khair NS, Mohammed SA (2021) A comparative study on the protective role of Silymarin and Coenzyme-Q10 on the cerebellar cortex of experimentally induced atherosclerosis in adult male albino rats: a histological, immunohistochemical and biochemical study. Egypt J Histol 44(2):322–338

    Google Scholar 

  31. Mancuso M, Orsucci D, Volpi L, Calsolaro V, Siciliano G (2010) Coenzyme Q10 in neuromuscular and neurodegenerative disorders. Curr Drug Targets 11(1):111–121

    Article  CAS  PubMed  Google Scholar 

  32. Spindler M, Beal MF, Henchcliffe C (2009) Coenzyme Q10 effects in neurodegenerative disease. Neuropsychiatr Dis Treat 5:597

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Vaselbehagh M, Sadegh M, Karami H, Babaie S (2021) Coenzyme Q10 modulates apoptotic effects of chronic administration of methadone on NMRI mouse hippocampus. Cell J (Yakhteh) 23:538–5435

    Google Scholar 

Download references

Acknowledgements

The authors are deeply grateful to colleagues and laboratory staff of NRC/IUMS for their sincere collaboration and Vice-Chancellor of Research and Technology (Grant No. 8811215292).

Funding

The present research is supported by the Neuroscience Research Center (NRC) of the Iran University of Medical Science.

Author information

Authors and Affiliations

Authors

Contributions

SBJ prepared the study design and budget planning as the PI of the project. MF, AK, ZS, SAB were involved in experiments and wrote the paper draft. SB and MJ collected the data, wrote first draft of the manuscript and edited. All the authors read and approved the final manuscript.

Corresponding author

Correspondence to M. Farhadi.

Ethics declarations

Conflict of interest

The authors have declared that no conflict of interest exist.

Ethical approval

The ethic committee for animal research of Neuroscience Research Center affiliated to Iran University of Medical Sciences approved all the procedures used in this study (Ethical Code IR.IUMS.REC.1396.32724).

Consent to participate

All authors participated in the informed consent.

Consent for publication

All authors approved publication.

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

Jameie, S.B., Kazemian, A., Sanadgol, Z. et al. Coenzyme Q10 reduces expression of apoptotic markers in adult rat nucleus accumbens dopaminergic neurons treated with methamphetamine. Mol Biol Rep 49, 2273–2281 (2022). https://doi.org/10.1007/s11033-021-07049-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-021-07049-7

Keywords

Navigation