Volume 11, Issue 1 (4-2013)                   IJRM 2013, 11(1): 39-46 | Back to browse issues page

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Mirjalili T, Kalantar S M, Shams Lahijani M, Sheikhha M H, Talebi A. Congenital abnormality effect of methamphetamine on histological, cellular and chromosomal defects in fetal mice. IJRM 2013; 11 (1) :39-46
URL: http://ijrm.ir/article-1-341-en.html
1- Developmental Biology, Animal Sciences, Faculty of Biological Sciences, Shahid Beheshti University, G.C., Tehran, Iran
2- Department of Medical Genetics, Research and Clinical Center for Infertility, Shahid Sadoughi University of Medical Sciences, Yazd, Iran , smkalantar@yahoo.com
3- Department of Medical Genetics, Research and Clinical Center for Infertility, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
4- Department of Andrology, Research and Clinical Center for Infertility, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
Abstract:   (2937 Views)
Background: Methamphetamine (MA) is a potent psychomotor stimulant with high abuse and addictive potential. MA is a neurotoxic drug which is widely abused by females of childbearing age, raising serious public health concerns in terms of exposure of the fetus to the drug. Neurotoxic effects of MA on adult are well known, such as dopaminergic nerve terminal degeneration and cell death in regions of brain in some doses.
Objective: In the present study, we examined effect of prenatal MA exposure on mouse fetuses.
Materials and Methods: In this study, forty 8-12 week-old NMRI female mice were used which were mated with male mice in serial days. When sperm plug was observed it was designated as gestational day (GD) 0. Pregnant mice were individually housed in plastic cages. Pregnant mice were divided into four groups: in first group 10 mg/kg /day MA, in second group 5 mg/kg /day MA and in third group saline were injected subcutaneously from GD 6 to GD 14, corresponding to organogenesis period, while fourth or control group were without injection. On GD 14 fetuses were removed and accomplished chromosome preparation from fetal liver. Then fetal were fixed in formalin for brain hematoxilin and eosine staining and TUNEL assay.
Results: We observed morphological abnormality including exencephal fetus in 5mg/kg MA group and premature fetuses in 10 mg/kg MA group. Also brain histological study showed subarachnoid hemorrhage in fetal brain in both experimental groups. Fetal liver karyotyping analysis was normal in fetuses of all groups and TUNEL assay in fetal striatum did not show significant difference in number of apoptotic cells between groups.
Conclusion: From our results, it could be concluded that chronic abuse of MA by pregnant females during organogenesis period can cause teratogenic effect and brain hemorrage in fetus.
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1. Vega WA, Kolody B, Hwang J, Noble A. Prevalence and magnitude of perinatal substance exposures in California see comments. N Engl J Med 1993; 329: 850-854. [DOI:10.1056/NEJM199309163291207]
2. Madras BK. A Novel Receptor Mechanism for Methamphetamine. Available at: http://www.hms.har vard.edu/NEPRC/contact.html">Contact=sNEPRS.
3. Plessinger MA.Prenatal exposure to amphetamines. Risks and adverse outcomes in pregnancy. Obstet Gynecol Clin North Am 1998; 25: 119-138.
4. Ricuarte G A, Schuster CR, Seiden LS. Long-term effects of repeated methyl amphetamine administration on dopamine and serotonin neurons in the rat brain: A regional study. Brain Res 1980; 19: 153-163. [DOI:10.1016/0006-8993(80)90952-X]
5. Wagner GC, Ricuarte GA, Seiden LS, Schuster CR, Miller RJ, Westley J. Long-lasting depletions of striatal dopamine and loss of dopamine uptake sites following repeated administration methamphetamine. Brain Res 1980; 181: 151-160. [DOI:10.1016/0006-8993(80)91265-2]
6. Xie T, McCann UD, Kim SY, Ricaurte GA. Effect of temperature on dopamine transporter function and intracellular accumulation of methamphetamine: Implications for methamphetamine- induced dopaminergic neurotoxicity. J Neurosci 2000; 20: 7838-7845.
7. Brown JM, Riddle EL, Sandoval V, Weston RK, Hanson JE, Crosby MJ, et al. A single methamphetamine administration rapidly decreases vesicular dopamine uptake. J Pharmacol Exp Ther 2002; 302: 497-501. [DOI:10.1124/jpet.302.2.497]
8. Callahan BT, Cord BJ, Yuan J, McCann UD, Ricaurte GA. Inhibitors of Na (+) / H (+) and Na (+) / Ca (2+) exchange potentiate methamphetamine-induced dopamine neurotoxicity: possible role of ionic dysregulation in methamphetamine neurotoxicity. J Neurochem 2001; 77: 1348-1362. [DOI:10.1046/j.1471-4159.2001.00341.x]
9. Kogan FJ, Nichols WK, Gibb JW. Influence of methamphetamine on nigral and striatal tyrosine hydroxylase activity and on striatal dopamine levels. Eur J Pharmacol 1976; 36: 363-371. [DOI:10.1016/0014-2999(76)90090-X]
10. Bakhit C, Gibb JW. Methamphetamine-induced depression of tryptophan hydroxylase: Recovery following acute treatment. Eur J Pharmacol 1981; 76: 229-233.
11. Trulson ME, Trulson VM. Effects of chronic methamphetamine administration on tryptophan hydroxylase activity, [3H] serotonin synaptosomal uptake, and serotonin metabolism in rat brain following systemic tryptophan loading. Neuropharmacol 1982; 21: 521-527. [DOI:10.1016/0028-3908(82)90042-9]
12. Schmued LC, Bowyer JF. Methamphetamine exposure can produce neuronal degeneration in mouse hippocampal remnants. Brain Res 1997; 759: 135-140.
13. Thiriet N, Deng X, Solinas M, Ladenheim B, Curtis W, Goldberg SR, et al. Neuropeptide Y Protects against Methamphetamine-Induced Neuronal Apoptosis in the Mouse Striatum. J Neurosci 2005; 25: 5273-5279. [DOI:10.1523/JNEUROSCI.4893-04.2005]
14. Pu C, Broening HW, Vorhees CV. Effect of methamphetamine on glutamate-positive neurons in the adult and developing rat somatosensory cortex. Synapse 1998; 23: 328-334. https://doi.org/10.1002/(SICI)1098-2396(199608)23:4<328::AID-SYN11>3.0.CO;2-T [DOI:10.1002/(SICI)1098-2396(199608)23:43.0.CO;2-T]
15. Jeng W, Ramkissoon A, Parman T, Wells PG. Prostaglandin H synthase-catalyzed bioactivation of amphetamines to free radical intermediates that cause CNS regional DNA oxidation and nerve terminal degeneration. FASEB J 2006; 20: 638-650. [DOI:10.1096/fj.05-5271com]
16. Volkow ND, Chang L, Wang GJ, Fowler JS, Franceschi D, Sedler M, et al. Loss of dopamine transporters in methamphetamine abusers recovers with protracted abstinence. J Neurosci 2001; 21: 9414-9418.
17. Henry BL, Minassian A, Perry W. Effect of methamphetamine dependence on everyday functional ability. Addict behav 2010; 35: 1873-1877. [DOI:10.1016/j.addbeh.2010.01.013]
18. Williams MT, Moran MS, Vorhees CV, Refining the critical period for methamphetamine-induced spatial deficits in the Morris water maze. Psychopharmacology. Synapse 2003; 168: 329-338.
19. Chaudhuri C, Salahudeen AK. Massive intracerebral hemorrhage in an amphetamine addict. Am J Med Sci 1999; 317: 350-352. [DOI:10.1016/S0002-9629(15)40539-7]
20. Jacobs LJ. Reversible dilated cardiomyopathy induced by methamphetamine. Clin Cardiol 1989; 12: 725–727. [DOI:10.1002/clc.4960121211]
21. Marcondes MC, Flynn C, Watry DD, Zandonatti M. Fox HS. Methamphetamine Increases Brain Viral Load and Activates Natural Killer Cells in Simian Immunodeficiency Virus-Infected Monkeys. Am J Pathol 2010; 43: 1525-1528. [DOI:10.2353/ajpath.2010.090953]
22. Matera RF, Zabala H, Jimenez AP. Bifid exencephalia. Teratogen action of amphetamine. Int Surg 1968; 50: 79-85.
23. Little BB, Snell LM, Gilstrap LC. Methamphetamine abuse during pregnancy: Outcome and fetal effects. Obstet Gynecol 1988; 72: 541-544.
24. Dixon SD, Bejar R. Echoencephalographic findings in neonates associated with maternal cocaine and methamphetamine use: Incidence and clinical correlates. J Pediatr 1989; 115: 770-778. [DOI:10.1016/S0022-3476(89)80661-4]
25. Thomas DB. Cleft palate, mortality and morbidity in infants of substance abusing mothers. J Paediatr Child Health 1995; 31: 457-460. [DOI:10.1111/j.1440-1754.1995.tb00857.x]
26. Nora JJ, Vargo TA, Nora AH, Love KE, McNamara DG. Dexamphetamine: A possible environmental trigger in cardiovascular malformations. Lancet 1970; 1: 1290-1291. [DOI:10.1016/S0140-6736(70)91765-4]
27. Bendure W, Raman R, Palmer S. Exencephaly in a neonate exposed prenatally to methamphetamine and the toxic. Available at: http://www.acmg.net/ resources/ACMG/2005/abs-group-14.pdf.
28. Chang L, Smith L, LoPresti C, Yonekura M, Kuo J, Walot I, et al. Smaller subcortical volumes and cognitive deficits in children with prenatal methamphetamine exposure. Psychiatr Res 132: 95-106.
29. Yamamoto Y, Yamamoto K, Fukui Y, Kurishita A. Teratogenic effects of methamphetamine in mice. NCBI 1992; 46: 126-131.
30. Acuff-Smith KD, Schilling MA, Fisher JE, Vorhees CV, Stagespecific effects of prenatal d-methamphetamine exposure on behavioral and eye development in rats. Neurotoxicol Teratol 1996; 18: 199-215. [DOI:10.1016/0892-0362(95)02015-2]
31. Slamberova R, Pometlova M, Charousova P. Postnatal development of rat pups is altered by prenatal methamphetamine exposure. Prog Neuro Psycho Pharmacol Biol Psychiatry 2006; 30: 82-88. [DOI:10.1016/j.pnpbp.2005.06.006]
32. Cui C, Sakata-Haga H, Ohta K, Nishida M, Yashiki M, Sawada K, et al. Histological brain alterations following prenatal methamphetamine exposure in rats. Congenit Anomal 2006; 46:180-187. [DOI:10.1111/j.1741-4520.2006.00126.x]
33. Yamamoto Y, Yamamoto K. The Teratogenicity of Methamphetamine is Influenced by Housing Conditions of Pregnant Mice. Congenit Anomal 2008; 34: 337-343. [DOI:10.1111/j.1741-4520.1994.tb00803.x]
34. Bendure W, Raman R, Palmer S. Exencephaly in a neonate exposed prenatally to methamphetamine and the toxic chemicals of a clandestine home methamphetamine laboratory environment. Available at :http://www.acmg.net/resources/ACMG/2005/abs-group-14.pdf.
35. Tsai EM, Lee JN, Chao MC, Chai CY. Holoprosencephaly and trisomy 13 in a fetus with maternal early gestational amphetamine abuse-a case report. Gaoxiong Yi Xue Ke Xue Za Zhi 1993; 9: 703-706.
36. Dixon SD, Bejar R. Echoencephalographic findings in neonates associated with maternal cocaine and methamphetamine use: Incidence and clinical correlates. J Pediatr 1989; 115: 770-778. [DOI:10.1016/S0022-3476(89)80661-4]
37. Kolesari GL, Kaplan S. Amphetamines reduce embryonic size and produce caudal hematomas during early chick morphogenesis. Teratology 1979; 20: 403-412. [DOI:10.1002/tera.1420200311]
38. Stek AM, Baker RS, Fisher BK, Lang U, Clark KE. Fetal responses to maternal and fetal methamphetamine administration in sheep. Am J Obstet Gynecol 1995; 173: 1592-1598. [DOI:10.1016/0002-9378(95)90654-1]
39. Jain M, Armstrong RJ, Barker RA, Rosser AE. Cellular and molecular aspects of striatal development. Brain Res Bullet 2001; 55: 533-540. [DOI:10.1016/S0361-9230(01)00555-X]
40. Fentress JC, Stanfield BB, Cowan WM. Observations on the development of the striatum in mice and rats. Anat Embryol 1981; 163: 275-298. [DOI:10.1007/BF00315705]
41. Wong AW, McCallum GP, Jeng W, Wells PG. Oxoguanine Glycosylase 1 Protects Against Methamphetamine-Enhanced Fetal Brain Oxidative DNA Damage and Neurodevelopmental Deficits. J Neurosci 2008; 28: 9047-9054. [DOI:10.1523/JNEUROSCI.2557-08.2008]
42. Tokunaga I, Ishigami A, Kubo S, Gotohda T, Kitamura O. The peroxidative DNA damage and apoptosis in methamphetamine-treated rat brain. J Med Invest 2008; 55: 241-245. [DOI:10.2152/jmi.55.241]

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