Skip to main content
SpringerLink
Log in

Effects of methamphetamine in the hippocampus of cynomolgus monkeys according to age

  • Original Article
  • Published:
BioChip Journal Aims and scope Submit manuscript

Abstract

The aim of this study was to investigate differentially expressed genes (DEGs) and their functions in the hippocampi after methamphetamine (MA) administration in cynomolgus macaques according to age. Cynomolgus monkeys were divided by age as follows: control, 6–12 months (age 1, A1), 3–4 (A2) years, 7–9 (A3) years, and more than 11 years (A4). After MA was injected into the monkeys (2 mg/kg, intramuscular injection in each of A1, A2, A3 and A4), we performed large-scale transcriptome profiling in the hippocampus. Some genes associated with neuron differentiation, development, and transmission were validated with real-time RT-PCR. The expression patterns of validated genes were also investigated in the hippocampi of monkeys one year after a single injection of MA. The correlation of DEGs between A2 and A3 animals, who are similar to humans in early teens to early twenties, was higher than that of other groups, showing the possibility that biological mechanisms in the hippocampus of A2 and A3 are similarly affected by MA. Genes associated with neuron differentiation (FEZF1, GPR1N1, DLX1, and KCNIP2), neuron (projection) development (NGFR, CDKN1C, and VAX2), and synaptic transmission (SYT4, SYT1, GAD2, CORT, and NPTX2) were differentially expressed among control and MA-treated animals. In particular, the expression patterns of GPR1N1 among control and MA-treated animals following a single injection of MA were not altered even one year after single MA administration. Our results suggest that genes associated with neuron differentiation and synaptic transmission in the hippocampus of different maturation stages are differentially regulated by MA.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Herman-Stahl, M.A., Krebs, C.P., Kroutil, L.A. & Heller, D.C. Risk and protective factors for methamphetamine use and nonmedical use of prescription stimulants among young adults aged 18 to 25. Addict. Behav. 32, 1003–1015 (2007).

    Article  Google Scholar 

  2. Kim, K.Y. et al. The first application of wastewaterbased drug epidemiology in five South Korean cities. Sci. Total Environ. 524-525, 440–446 (2015).

    Article  CAS  Google Scholar 

  3. SPO. The 2008 statistics on Supreme Prosecutors’ Office. Available at: http://www.spo.go.kr/eng/procedure/cp.jsp. (2008).

    Google Scholar 

  4. Izenwasser, S. Differential effects of psychoactive drugs in adolescents and adults. Crit. Rev. Neurobiol. 17, 51–67 (2005).

    Article  CAS  Google Scholar 

  5. Kalechstein, A.D., Newton, T.F. & Green, M. Methamphetamine dependence is associated with neurocognitive impairment in the initial phases of abstinence. J. Neuropsychiatry Clin. Neurosci. 15, 215–220 (2003).

    Article  CAS  Google Scholar 

  6. Nordahl, T.E., Salo, R. & Leamon, M. Neuropsychological effects of chronic methamphetamine use on neurotransmitters and cognition: a review. J. Neuropsychiatry Clin. Neurosci. 15, 317–325 (2003).

    Article  CAS  Google Scholar 

  7. Jayanthi, S. et al. Methamphetamine induces dopamine D1 receptor-dependent endoplasmic reticulum stressrelated molecular events in the rat striatum. PLoS One 4,e6092 (2009).

    Article  Google Scholar 

  8. Jing, L. et al. Comparison of single versus repeated methamphetamine injection induced behavioral sensitization in mice. Neurosci. Lett. 560, 103–106 (2014).

    Article  CAS  Google Scholar 

  9. Morrow, B.A., Roth, R.H., Redmond, D.E. & Elsworth, J.D. Impact of methamphetamine on dopamine neurons in primates is dependent on age: implications for development of Parkinson’s disease. Neuroscience 189, 277–285 (2011).

    Article  CAS  Google Scholar 

  10. Truong, J.G. et al. Age-dependent methamphetamineinduced alterations in vesicular monoamine transporter-2 function: implications for neurotoxicity. J. Pharmacol. Exp. Ther. 314, 1087–1092 (2005).

    Article  CAS  Google Scholar 

  11. Miller, D.B., O’Callaghan, J.P. & Ali, S.F. Age as a susceptibility factor in the striatal dopaminergic neurotoxicity observed in the mouse following substituted amphetamine exposure. Ann. N. Y. Acad. Sci. 914, 194–207 (2000).

    Article  CAS  Google Scholar 

  12. Good, R.L., Liang, L.P., Patel, M. & Radcliffe, R.A. Mouse strain- and age-dependent effects of binge methamphetamine on dopaminergic signaling. Neurotoxicology 32, 751–759 (2011).

    Article  CAS  Google Scholar 

  13. Cadet, J.L. & Brannock, C. Free radicals and the pathobiology of brain dopamine systems. Neurochem. Int. 32, 117–131 (1998).

    Article  CAS  Google Scholar 

  14. Zakharova, E., Leoni, G., Kichko, I. & Izenwasser, S. Differential effects of methamphetamine and cocaine on conditioned place preference and locomotor activity in adult and adolescent male rats. Behav. Brain Res. 198, 45–50 (2009).

    Article  CAS  Google Scholar 

  15. Veeranagouda, Y. et al. Identification of microRNAs in Macaca fascicularis (Cynomolgus Monkey) by Homology Search and Experimental Validation by Small RNASeq and RT-qPCR Using Kidney Cortex Tissues. PLoS One 10, e0142708 (2015).

    Article  Google Scholar 

  16. Weerts, E.M., Fantegrossi, W.E. & Goodwin, A.K. The value of nonhuman primates in drug abuse research. Exp. Clin. Psychopharmacol. 15, 309–327 (2007).

    Article  CAS  Google Scholar 

  17. Heo, J.H. et al. Spatial distribution of glucose hypometabolism induced by intracerebroventricular streptozotocin in monkeys. J. Alzheimers Dis. 25, 517–523 (2011).

    Google Scholar 

  18. Kofler, J. et al. Preventive immunization of aged and juvenile non-human primates to beta-amyloid. J. Neuroinflammation 9, 84 (2012).

    Article  CAS  Google Scholar 

  19. Uchida, A. et al. Non-human primate model of amyotrophic lateral sclerosis with cytoplasmic mislocalization of TDP-43. Brain 135, 833–846 (2012).

    Article  Google Scholar 

  20. Barbisin, M. et al. Gene expression profiling of brains from bovine spongiform encephalopathy (BSE)-infected cynomolgus macaques. BMC Genomics 15, 434 (2014).

    Article  Google Scholar 

  21. Eyster, K., Appt, S., Chalpe, A., Register, T. & Clarkson, T. Effects of equol on gene expression in female cynomolgus monkey iliac arteries. Nutr. Metab. Cardiovasc. Dis. 24, 423–427 (2014).

    Article  CAS  Google Scholar 

  22. Lazarov, O. & Hollands, C. Hippocampal neurogenesis: Learning to remember. Prog. Neurobiol. 138-140, 1–18 (2016).

    Article  Google Scholar 

  23. Grant, S., Contoreggi, C. & London, E.D. Drug abusers show impaired performance in a laboratory test of decision making. Neuropsychologia 38, 1180–1187 (2000).

    Article  CAS  Google Scholar 

  24. Teuchert-Noodt, G., Dawirs, R.R. & Hildebrandt, K. Adult treatment with methamphetamine transiently decreases dentate granule cell proliferation in the gerbil hippocampus. J. Neural. Transm. (Vienna) 107, 133–143 (2000).

    Article  CAS  Google Scholar 

  25. Mandyam, C.D. et al. Varied access to intravenous methamphetamine self-administration differentially alters adult hippocampal neurogenesis. Biol. Psychiatry 64, 958–965 (2008).

    Article  CAS  Google Scholar 

  26. Baptista, S. et al. Methamphetamine decreases dentate gyrus stem cell self-renewal and shifts the differentiation towards neuronal fate. Stem Cell Res. 13, 329–341 (2014).

    Article  CAS  Google Scholar 

  27. Gonzalez-Rey, E. & Delgado, M. Cortistatin as a potential multistep therapeutic agent for inflammatory disorders. Drug News Perspect. 19, 393–399 (2006).

    Article  Google Scholar 

  28. Deng, X., Wang, Y., Chou, J. & Cadet, J.L. Methamphetamine causes widespread apoptosis in the mouse brain: evidence from using an improved TUNEL histochemical method. Brain Res. Mol. Brain Res. 93, 64–69 (2001).

    Article  CAS  Google Scholar 

  29. Zhu, J., Xu, W., Wang, J., Ali, S.F. & Angulo, J.A. The neurokinin-1 receptor modulates the methamphetamineinduced striatal apoptosis and nitric oxide formation in mice. J. Neurochem. 111, 656–668 (2009).

    Article  CAS  Google Scholar 

  30. Laviola, G., Adriani, W., Terranova, M.L. & Gerra, G. Psychobiological risk factors for vulnerability to psychostimulants in human adolescents and animal models. Neurosci. Biobehav. Rev. 23, 993–1010 (1999).

    Article  CAS  Google Scholar 

  31. Kalivas, P.W. The glutamate homeostasis hypothesis of addiction. Nat. Rev. Neurosci. 10, 561–572 (2009).

    Article  CAS  Google Scholar 

  32. Chen, C. et al. Role of PUMA in methamphetamineinduced neuronal apoptosis. Toxicol. Lett. 240, 149–160 (2016).

    Article  CAS  Google Scholar 

  33. Baptista, S. et al. Neuropeptide Y promotes neurogenesis and protection against methamphetamine-induced toxicity in mouse dentate gyrus-derived neurosphere cultures. Neuropharmacology 62, 2413–2423 (2012).

    Article  CAS  Google Scholar 

  34. Tulloch, I.K. et al. Methamphetamine induces low levels of neurogenesis in striatal neuron subpopulations and differential motor performance. Neurotox. Res. 26, 115–129 (2014).

    Article  CAS  Google Scholar 

  35. Dai, X., Iwasaki, H., Watanabe, M. & Okabe, S. Dlx1 transcription factor regulates dendritic growth and postsynaptic differentiation through inhibition of neuropilin-2 and PAK3 expression. Eur. J. Neurosci. 39, 531–547 (2014).

    Article  Google Scholar 

  36. Jones, D.L., Howard, M.A., Stanco, A., Rubenstein, J.L. & Baraban, S.C. Deletion of Dlx1 results in reduced glutamatergic input to hippocampal interneurons. J. Neurophysiol. 105, 1984–1991 (2011).

    Article  Google Scholar 

  37. Cobos, I. et al. Mice lacking Dlx1 show subtype-specific loss of interneurons, reduced inhibition and epilepsy. Nat. Neurosci. 8, 1059–1068 (2005).

    Article  CAS  Google Scholar 

  38. Eibl, J.K., Strasser, B.C. & Ross, G.M. Structural, biological, and pharmacological strategies for the inhibition of nerve growth factor. Neurochem. Int. 61, 1266–1275 (2012).

    Article  CAS  Google Scholar 

  39. Fei, D., Huang, T. & Krimm, R.F. The neurotrophin receptor p75 regulates gustatory axon branching and promotes innervation of the tongue during development. Neural Dev. 9, 15 (2014).

    Article  Google Scholar 

  40. Kraemer, B.R. et al. A role for the p75 neurotrophin receptor in axonal degeneration and apoptosis induced by oxidative stress. J. Biol. Chem. 289, 21205–21216 (2014).

    Article  Google Scholar 

  41. Ramkissoon, A. & Wells, P.G. Methamphetamine oxidative stress, neurotoxicity, and functional deficits are modulated by nuclear factor-E2-related factor 2. Free Radic. Biol. Med. 89, 358–368 (2015).

    Article  CAS  Google Scholar 

  42. de Lecea, L. et al. A cortical neuropeptide with neuronal depressant and sleep-modulating properties. Nature 381, 242–245 (1996).

    Article  Google Scholar 

  43. Broglio, F. et al. Ghrelin secretion is inhibited by either somatostatin or cortistatin in humans. J. Clin. Endocrinol. Metab. 87, 4829–4832 (2002).

    Article  CAS  Google Scholar 

  44. Shi, Z.Y. et al. Cortistatin Improves Cardiac Function After Acute Myocardial Infarction in Rats by Suppressing Myocardial Apoptosis and Endoplasmic Reticulum Stress. J. Cardiovasc. Pharmacol. Ther. pii: 1074248416644988 (2016).

    Google Scholar 

  45. Mendez-Diaz, M., Guevara-Martinez, M., Alquicira, C.R., Guzman Vasquez, K. & Prospero-Garcia, O. Cortistatin, a modulatory peptide of sleep and memory, induces analgesia in rats. Neurosci. Lett. 354, 242–244 (2004).

    Article  CAS  Google Scholar 

  46. Gresl, T.A. et al. Dietary restriction and glucose regulation in aging rhesus monkeys: a follow-up report at 8.5 yr. Am. J. Physiol. Endocrinol. Metab. 281, E757–765 (2001).

    Article  CAS  Google Scholar 

  47. Yeo, H.G. et al. Characterization of Cerebral Damage in a Monkey Model of Alzheimer’s Disease Induced by Intracerebroventricular Injection of Streptozotocin. J. Alzheimers Dis. 46, 989–1005 (2015).

    Article  CAS  Google Scholar 

  48. Trapnell, C. et al. Transcript assembly and quantification by RNA-Seq reveals unannotated transcripts and isoform switching during cell differentiation. Nat. Biotechnol. 28, 511–515 (2010).

    Article  CAS  Google Scholar 

  49. Choi, M.R. et al. Ethanol-induced small heat shock protein genes in the differentiation of mouse embryonic neural stem cells. Arch. Toxicol. 85, 293–304 (2011).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Psychiatry, Seoul St. Mary’s Hospital, The Catholic University of Korea College of Medicine, Seoul, Republic of Korea

    Mi Ran Choi, Sol Hee Bang & Dai-Jin Kim

  2. National Primate Research Center (NPRC), Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongju, Republic of Korea

    Yeung-Bae Jin, Youngjeon Lee, Han-Na Kim, Kyu-Tae Chang & Sang-Rae Lee

  3. Department of Functional Genomics, University of Science and Technology, Daejeon, Republic of Korea

    Kyu-Tae Chang & Sang-Rae Lee

  4. Department of Molecular and Life Sciences, Hanyang University, Ansan, Republic of Korea

    Kyoung Hwa Jung

Authors
  1. Mi Ran Choi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sol Hee Bang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yeung-Bae Jin
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Youngjeon Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Han-Na Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Kyu-Tae Chang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Kyoung Hwa Jung
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Sang-Rae Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Dai-Jin Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Sang-Rae Lee or Dai-Jin Kim.

Electronic supplementary material

13206_2017_1403_MOESM1_ESM.pdf

Supplementary file 2. IPA network analysis regulated by methamphetamine among different age groups. (a) Network of comparison between A2 and A1 (score: 6). (b) Network of comparison between A3 and A1 (score: 44). (c) Network of comparison between A4 and A1 (score: 42). (d) Network of comparison between A3 and A2. (e) Network of comparison between A4 and A2. (f) Network of comparison between A4 and A3. The intensity of the node (gene or gene products) color indicates the degree of up- (red) or down- (green) regulation.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Choi, M.R., Bang, S.H., Jin, YB. et al. Effects of methamphetamine in the hippocampus of cynomolgus monkeys according to age. BioChip J 11, 272–285 (2017). https://doi.org/10.1007/s13206-017-1403-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13206-017-1403-9

Keywords

Search

Navigation