Methamphetamine-Triggered Neurotoxicity in Human Dorsolateral Prefrontal Cortex

  • Ali Zare 1. Young Researchers and Elite Club, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
  • Alireza Ghanbari 1. Young Researchers and Elite Club, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
  • Mohammad Javad Hoseinpour 1. Young Researchers and Elite Club, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
  • Mahdi Eskandarian Boroujeni 2. Department of Stem Cells and Regenerative Medicine, Faculty of Medical Biotechnology, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran
  • Alimohammad Alimohammadi 3. Iranian Legal Medicine Organization, Tehran, Iran
  • Mohammad Amin Abdollahifar 4. Biology and Anatomical Sciences Department, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  • Abbas Aliaghaei 4. Biology and Anatomical Sciences Department, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  • Vahid Mansouri 5. Faculty of Paramedical Science, Proteomics Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  • Hamid Zaferani Arani 1. Young Researchers and Elite Club, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
DOI: https://doi.org/10.31661/gmj.v10i0.2016
Keywords: Methamphetamine; Prefrontal Cortex; Apoptosis; BDNF

Abstract

Background: Methamphetamine (MA), is an extremely addictive stimulant that adversely affects the central nervous system. Accumulating evidence indicates that molecular mechanisms such as oxidative stress, apoptosis, and autophagy are involved in the toxicity of MA. Considering experimental animal studies exhibiting MA-induced neurotoxicity, the relevance of these findings needs to be evidently elucidated in human MA users. It is generally assumed that multiple chemical substances released in the brain following MA-induced metabolic activation are primary factors underlying damage of neural cells. Hence, this study aimed to investigate the role of autophagy and apoptosis as well as oxidative stress in the brain of postmortem MA-induced toxicity. Materials and Methods: In this study, we determine the gene expression of autophagy and apoptosis, including BECN1, MAP1ALC3, CASP8, TP53, and BAX genes in ten healthy controls and ten chronic users of MA postmortem dorsolateral prefrontal cortex (DLPFC) by real-time polymerase chain reaction. Also, we applied immunohistochemistry in formalin-fixed and paraffin-embedded human brain samples to analyze brain-derived neurotrophic factor (BDNF). Also, spectrophotometry was performed to measure glutathione (GSH) content. Results: The expression level of apoptotic and autophagic genes (BECN1, MAP1ALC3, CASP8, TP53, and BAX) were significantly elevated, while GSH content and BDNF showed substantial reductions in DLPFC of chronic MA users. Conclusion: Our data showed that MA addiction provokes transduction pathways, namely apoptosis and autophagy, along with oxidative mechanisms in DLPFC. Also, MA induces multiple functional and structural perturbations in the brain, determining its toxicity and possibly contributing to neurotoxicity. [GMJ.2021;10:e2016]

References

Rommel N, Rohleder NH, Wagenpfeil S, Härtel-Petri R, Jacob F, Wolff K-D, et al. The impact of the new scene drug "crystal meth" on oral health: a case-control study. Clin Oral Investig. 2016;20(3):469-75.

https://doi.org/10.1007/s00784-015-1527-z

PMID: 26174081

Kish SJ. Pharmacologic mechanisms of crystal meth. Can Med Assoc J. 2008;178(13):1679-82.

https://doi.org/10.1503/cmaj.071675

PMID: 18559805 PMCID: PMC2413312

Volkow ND, Fowler JS, Wang G-J, Shumay E, Telang F, Thanos PK, et al. Distribution and pharmacokinetics of methamphetamine in the human body: clinical implications. PLoS One. 2010;5(12):e15269.

https://doi.org/10.1371/journal.pone.0015269

PMID: 21151866 PMCID: PMC2998419

Schep LJ, Slaughter RJ, Beasley DMG. The clinical toxicology of metamfetamine. Clin Toxicol. 2010;48(7):675-94.

https://doi.org/10.3109/15563650.2010.516752

PMID: 20849327

Ares-Santos S, Granado N, Espadas I, Martinez-Murillo R, Moratalla R. Methamphetamine causes degeneration of dopamine cell bodies and terminals of the nigrostriatal pathway evidenced by silver staining. Neuropsychopharmacology. 2014;39(5):1066.

https://doi.org/10.1038/npp.2013.307

PMID: 24169803 PMCID: PMC3957101

Morrow BA, Roth RH, Redmond DE, Elsworth JD. Impact of methamphetamine on dopamine neurons in primates is dependent on age: implications for development of Parkinson's disease. Neuroscience. 2011;189:277-85.

https://doi.org/10.1016/j.neuroscience.2011.05.046

PMID: 21640165 PMCID: PMC3150352

Rose ME, Grant JE. Pharmacotherapy for methamphetamine dependence: a review of the pathophysiology of methamphetamine addiction and the theoretical basis and efficacy of pharmacotherapeutic interventions. Ann Clin Psychiatry. 2008;20(3):145-55.

https://doi.org/10.1080/10401230802177656

PMID: 18633741

Möbius C, Kustermann A, Struffert T, Kornhuber J, Müller HH. c-MRI findings after crystal meth abuse. J Addict Med. 2014;8(5):384-5.

https://doi.org/10.1097/ADM.0000000000000051

PMID: 25026102

Callaghan RC, Cunningham JK, Sykes J, Kish SJ. Increased risk of Parkinson's disease in individuals hospitalized with conditions related to the use of methamphetamine or other amphetamine-type drugs. Drug Alcohol Depend. 2012;120(1-3):35-40.

https://doi.org/10.1016/j.drugalcdep.2011.06.013

PMID: 21794992

Hoshi E. Functional specialization within the dorsolateral prefrontal cortex: a review of anatomical and physiological studies of non-human primates. Neurosci Res. 2006;54(2):73-84.

https://doi.org/10.1016/j.neures.2005.10.013

PMID: 16310877

Klaus J, Schutter DJ. The Role of Left Dorsolateral Prefrontal Cortex in Language Processing. Neuroscience. 2018;377:197-205.

https://doi.org/10.1016/j.neuroscience.2018.03.002

PMID: 29534975

Yamamoto DJ, Woo C-W, Wager TD, Regner MF, Tanabe J. Influence of dorsolateral prefrontal cortex and ventral striatum on risk avoidance in addiction: a mediation analysis. Drug Alcohol Depend. 2015;149:10-7.

https://doi.org/10.1016/j.drugalcdep.2014.12.026

PMID: 25736619 PMCID: PMC4361089

Goldstein RZ, Volkow ND. Dysfunction of the prefrontal cortex in addiction: neuroimaging findings and clinical implications. Nature reviews neuroscience. 2011;12(11):652.

https://doi.org/10.1038/nrn3119

PMID: 22011681 PMCID: PMC3462342

Yu S, Zhu L, Shen Q, Bai X, Di X. Recent advances in methamphetamine neurotoxicity mechanisms and its molecular pathophysiology. Behav Neurol. 2015; 2015.

https://doi.org/10.1155/2015/103969

PMID: 25861156 PMCID: PMC4377385

Roohbakhsh A, Shirani K, Karimi G. Methamphetamine-induced toxicity: The role of autophagy? Chem Biol Interact. 2016;260:163-7.

https://doi.org/10.1016/j.cbi.2016.10.012

PMID: 27746146

Wu A, Ying Z, Gomez‐Pinilla F. The interplay between oxidative stress and brain‐derived neurotrophic factor modulates the outcome of a saturated fat diet on synaptic plasticity and cognition. Eur J Neurosci. 2004;19(7):1699-707.

https://doi.org/10.1111/j.1460-9568.2004.03246.x

PMID: 15078544

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

https://doi.org/10.1016/j.lfs.2013.07.014

PMID: 23892199 PMCID: PMC3870191

Volkow N, Fowler J, Wang G, Baler R, Telang F. Imaging dopamine's role in drug abuse and addiction. Neuropharmacology. 2009;56:3-8.

https://doi.org/10.1016/j.neuropharm.2008.05.022

PMID: 18617195 PMCID: PMC2696819

Sekine Y, Minabe Y, Ouchi Y, Takei N, Iyo M, Nakamura K, et al. Association of dopamine transporter loss in the orbitofrontal and dorsolateral prefrontal cortices with methamphetamine-related psychiatric symptoms. Am J Psychiatry. 2003;160(9):1699-701.

https://doi.org/10.1176/appi.ajp.160.9.1699

PMID: 12944350

Larsen KE, Fon EA, Hastings TG, Edwards RH, Sulzer D. Methamphetamine-induced degeneration of dopaminergic neurons involves autophagy and upregulation of dopamine synthesis. J Neurosci. 2002;22(20):8951-60.

https://doi.org/10.1523/JNEUROSCI.22-20-08951.2002

PMID: 12388602 PMCID: PMC6757693

Fornai F, Lenzi P, Gesi M, Soldani P, Ferrucci M, Lazzeri G, et al. Methamphetamine produces neuronal inclusions in the nigrostriatal system and in PC12 cells. J Neurochem. 2004;88(1):114-23.

https://doi.org/10.1046/j.1471-4159.2003.02137.x

PMID: 14675155

Kanthasamy A, Anantharam V, Ali SF, Kanthasamy A. Methamphetamine induces autophagy and apoptosis in a mesencephalic dopaminergic neuronal culture model: role of cathepsin‐D in methamphetamine‐induced apoptotic cell death. Annals of the New York Academy of Sciences. 2006;1074(1):234-44.

https://doi.org/10.1196/annals.1369.022

PMID: 17105920

Quan L, Ishikawa T, Michiue T, Li D-R, Zhao D, Oritani S, et al. Ubiquitin-immunoreactive structures in the midbrain of methamphetamine abusers. Leg Med. 2005;7(3):144-50.

https://doi.org/10.1016/j.legalmed.2004.11.002

PMID: 15847821

Cadet JL, Jayanthi S, Deng X. Methamphetamine-induced neuronal apoptosis involves the activation of multiple death pathways. Review. Neurotox Res. 2005;8(3-4):199-206.

https://doi.org/10.1007/BF03033973

PMID: 16371314

Asanuma M, Miyazaki I, Higashi Y, Diaz-Corrales FJ, Shimizu M, Miyoshi K, et al. Suppression of p53-activated gene, PAG608, attenuates methamphetamine-induced neurotoxicity. Neurosci Lett. 2007;414(3):263-7.

https://doi.org/10.1016/j.neulet.2006.12.036

PMID: 17234339

Kowiański P, Lietzau G, Czuba E, Waśkow M, Steliga A, Moryś J. BDNF: a key factor with multipotent impact on brain signaling and synaptic plasticity. Cell Mol Neurobiol. 2018; 38(3):579-93.

https://doi.org/10.1007/s10571-017-0510-4

PMID: 28623429 PMCID: PMC5835061

Bathina S, Das UN. Brain-derived neurotrophic factor and its clinical implications. Archives of medical science: AMS. 2015;11(6):1164.

https://doi.org/10.5114/aoms.2015.56342

PMID: 26788077

Weickert C, Hyde T, Lipska B, Herman M, Weinberger D, Kleinman J. Reduced brain-derived neurotrophic factor in prefrontal cortex of patients with schizophrenia. Mol Psychiatry. 2003;8(6):592.

https://doi.org/10.1038/sj.mp.4001308

PMID: 12851636

Reinhart V, Bove SE, Volfson D, Lewis DA, Kleiman RJ, Lanz TA. Evaluation of TrkB and BDNF transcripts in prefrontal cortex, hippocampus, and striatum from subjects with schizophrenia, bipolar disorder, and major depressive disorder. Neurobiol Dis. 2015;77:220-7.

https://doi.org/10.1016/j.nbd.2015.03.011

PMID: 25796564

Jang EY, Yang CH, Hedges DM, Kim SP, Lee JY, Ekins TG, et al. The role of reactive oxygen species in methamphetamine self‐administration and dopamine release in the nucleus accumbens. Addict Biol. 2017;22(5):1304-15.

https://doi.org/10.1111/adb.12419

PMID: 27417190 PMCID: PMC5237425

Cadet JL, Krasnova IN. Molecular bases of methamphetamine-induced neurodegeneration. Int Rev Neurobiol. 2009;88:101-19.

https://doi.org/10.1016/S0074-7742(09)88005-7

PMID: 19897076 PMCID: PMC8247532

Kita T, Miyazaki I, Asanuma M, Takeshima M, Wagner GC. Dopamine-induced behavioral changes and oxidative stress in methamphetamine-induced neurotoxicity. Int Rev Neurobiol. 2009;88:43-64.

https://doi.org/10.1016/S0074-7742(09)88003-3

PMID: 19897074

Barayuga SM, Pang X, Andres MA, Panee J, Bellinger FP. Methamphetamine decreases levels of glutathione peroxidases 1 and 4 in SH-SY5Y neuronal cells: protective effects of selenium. Neurotoxicology. 2013;37:240-6.

https://doi.org/10.1016/j.neuro.2013.05.009

PMID: 23721877 PMCID: PMC3717519

Limanaqi F, Gambardella S, Biagioni F, Busceti CL, Fornai F. Epigenetic Effects Induced by Methamphetamine and Methamphetamine-Dependent Oxidative Stress. Oxid Med Cell Longev. 2018;2018:4982453.

https://doi.org/10.1155/2018/4982453

PMID: 30140365 PMCID: PMC6081569

Eskandarian Boroujeni M, Peirouvi T, Shaerzadeh F, Ahmadiani A, Abdollahifar MA, Aliaghaei A. Differential gene expression and stereological analyses of the cerebellum following methamphetamine exposure. Addict Biol. 2020 ;25(1):e12707.

https://doi.org/10.1111/adb.12707

PMID: 30714656

Published
2021-08-23
How to Cite
Zare, A., Ghanbari, A., Hoseinpour, M. J., Eskandarian Boroujeni, M., Alimohammadi, A., Abdollahifar, M. A., Aliaghaei, A., Mansouri, V., & Zaferani Arani, H. (2021). Methamphetamine-Triggered Neurotoxicity in Human Dorsolateral Prefrontal Cortex. Galen Medical Journal, 10, e2016. https://doi.org/10.31661/gmj.v10i0.2016
Issue
Vol. 10 (2021): Continuous volume in progress
Section
Original Article

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