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Vol. 79, No. 6, 2004
Issue release date: 2004

Dopamine Transporter as a Marker of Neuroprotection in Methamphetamine-Lesioned Mice Treated Acutely with Estradiol

D’Astous M. · Gajjar T.M. · Dluzen D.E. · Di Paolo T.
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Abstract

Our laboratories have shown the positive effect of estradiol on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine- and methamphetamine (MA)-induced striatal dopamine (DA) depletion. Most studies on E neuroprotection use chronic administration of the steroid to evaluate its beneficial effect. In the present report, we investigated the neuroprotective potential of 17β-estradiol-3-benzoate (E) under acute conditions when administered 24, 12 or 0.5 h before MA. The effects of E on striatal DA and dihydroxyphenylacetic acid (DOPAC) contents, and DA transporter (DAT) protein and mRNA were measured using high-performance liquid chromatography, autoradiography and in situ hybridization, respectively. We observed neuroprotection with an acute dose of E, and also that protection presents a different time course for each dopaminergic marker. DAT mRNA responded more quickly to E than its protein (at 0.5 h vs. 24 h). Also, E treatment 12 h prior to MA resulted in ‘normal’ (equal to control) DA content, while DAT protein was still decreased as compared to control values. These different responses for each marker may represent different mechanisms of action of E (genomic versus nongenomic). Since most experimental studies use DA content as the sole indicator of nigrostriatal toxicity and examine a single time point following chronic E administration, the present results demonstrate the importance of evaluating differences in temporally dependent responses of DA, DAT protein and mRNA, to achieve a more comprehensive indication of the nigrostriatal state and the means by which E can function as a neuroprotectant in this system.



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References

  1. Davidson C, Gow AJ, Lee TH, Ellinwood EH: Methamphetamine neurotoxicity: Necrotic and apoptotic mechanisms and relevance to human abuse and treatment. Brain Res Brain Res Rev 2001;36:1–22.
  2. Gerlach M, Riederer P: Animal models of Parkinson’s disease: An empirical comparison with the phenomenology of the disease in man. J Neural Transm 1996;103:987–1041.
  3. Gibb JW, Kogan FJ: Influence of dopamine synthesis on methamphetamine-induced changes in striatal and adrenal tyrosine hydroxylase activity. Naunyn Schmiedebergs Arch Pharmacol 1979;310:185–187.
  4. Ricaurte GA, Schuster CR, Seiden LS: Long-term effects of repeated methylamphetamine administration on dopamine and serotonin neurons in the rat brain: A regional study. Brain Res 1980;193:153–163.
  5. Wagner GC, Ricaurte GA, Seiden LS, Schuster CR, Miller RJ, Westley J: Long-lasting depletions of striatal dopamine and loss of dopamine uptake sites following repeated administration of methamphetamine. Brain Res 1980;181:151–160.
  6. Pu C, Vorhees CV: Developmental dissociation of methamphetamine-induced depletion of dopaminergic terminals and astrocyte reaction in rat striatum. Brain Res Dev Brain Res 1993;72:325–328.
  7. Dluzen DE, McDermott JL: Gender differences in neurotoxicity of the nigrostriatal dopaminergic system: Implications for Parkinson’s disease. J Gend Specif Med 2000;3:36–42.
  8. Wagner GC, Tekirian TL, Cheo CT: Sexual differences in sensitivity to methamphetamine toxicity. J Neural Transm Gen Sect 1993;93:67–70.
  9. Brooks WJ, Jarvis, MF, Wagner GC: Influence of sex, age and strain on MPTP-induced neurotoxicity. Res Commun Subst Abuse 1989;10:181–184.
  10. Dluzen DE, McDermott JL: Neuroprotective role of estrogen upon methamphetamine and related neurotoxins within the nigrostriatal dopaminergic system. Ann NY Acad Sci 2000;914:112–126.
  11. Gao X, Dluzen DE: Tamoxifen abolishes estrogen’s neuroprotective effect upon methamphetamine neurotoxicity of the nigrostriatal dopaminergic system. Neuroscience 2001;103:385–394.
  12. Dluzen DE, McDermott JL, Anderson LI: Tamoxifen diminishes methamphetamine-induced striatal dopamine depletion in intact female and male mice. J Neuroendocrinol 2001;13:618–624.
  13. Carli M, Morissette M, Hebert C, Di Paolo T, Reader TA: Effects of a chronic lithium treatment on central dopamine neurotransporters. Biochem Pharmacol 1997;54:391–397.
  14. Callier S, Morissette M, Grandbois M, Pelaprat D, Di Paolo T: Neuroprotective properties of 17beta-estradiol, progesterone, and raloxifene in MPTP C57Bl/6 mice. Synapse 2001;41:131–138.
  15. Franklin K, Paxinos G: The Mouse Brain in Stereotaxic Coordinates. San Diego, Academic, 1997.
  16. Callier S, Morissette M, Grandbois M, Di Paolo T: Stereospecific prevention by 17beta-estradiol of MPTP-induced dopamine depletion in mice. Synapse 2000;37:245–251.
  17. Rivest R, Falardeau P, Di Paolo T: Brain dopamine transporter: Gender differences and effect of chronic haloperidol. Brain Res 1995;692:269–272.
  18. Gajjar TM, Anderson LI, Dluzen DE: Acute effects of estrogen upon methamphetamine induced neurotoxicity of the nigrostriatal dopaminergic system. J Neural Transm 2003;110:1215–1224.
  19. Dluzen DE, McDermott JL: Estrogen, anti-estrogen, and gender: Differences in methamphetamine neurotoxicity. Ann NY Acad Sci 2002;965:136–156.
  20. Yu L, Liao PC: Estrogen and progesterone distinctively modulate methamphetamine-induced dopamine and serotonin depletions in C57BL/6J mice. J Neural Transm 2000;107:1139–1147.
  21. Zetterstrom T, Sharp T, Collin AK, Ungerstedt U: In vivo measurement of extracellular dopamine and DOPAC in rat striatum after various dopamine-releasing drugs; implications for the origin of extracellular DOPAC. Eur J Pharmacol 1988;148:327–334.
  22. Bywood PT, Johnson SM: Dendrite loss is a characteristic early indicator of toxin-induced neurodegeneration in rat midbrain slices. Exp Neurol 2000;161:306–316.
  23. Harvey DC, Lacan G, Melegan WP: Regional heterogeneity of dopaminergic deficits in vervet monkey striatum and substantia nigra after methamphetamine exposure. Exp Brain Res 2000;133:349–358.
  24. Romano GJ, Mobbs CV, Howells RD, Pfaff DW: Estrogen regulation of proenkephalin gene expression in the ventromedial hypothalamus of the rat: Temporal qualities and synergism with progesterone. Brain Res Mol Brain Res 1989;5:51–58.
  25. Behl C, Skutella T, Lezoualc’h F, Post A, Widmann M, Newton CJ, Holsboer F: Neuroprotection against oxidative stress by estrogens: Structure-activity relationship. Mol Pharmacol 1997;51:535–541.
  26. Green PS, Gordon K, Simpkins JW: Phenolic A ring requirement for the neuroprotective effects of steroids. J Steroid Biochem Mol Biol 1997;63:229–235.
  27. Green PS, Yang SH, Nilsson KR, Kumar AS, Covey DF, Simpkins JW: The nonfeminizing enantiomer of 17beta-estradiol exerts protective effects in neuronal cultures and a rat model of cerebral ischemia. Endocrinology 2001;142:400–406.
  28. Moosmann B, Behl C: The antioxidant neuroprotective effects of estrogens and phenolic compounds are independent from their estrogenic properties. Proc Natl Acad Sci USA 1999;96:8867–8872.
  29. Dluzen DE, Tweed C, Anderson LI, Laping NJ: Gender differences in methamphetamine-induced mRNA associated with neurodegeneration in the mouse nigrostriatal dopaminergic system. Neuroendocrinology 2003;77:232–238.
  30. Cappon GD, Pu C, Vorhees CV: Time-course of methamphetamine-induced neurotoxicity in rat caudate-putamen after single-dose treatment. Brain Res 2000;863:106–111.
  31. Wilson JM, Kalasinsky KS, Levey AI, Bergeron C, Reiber G, Anthony RM, Schmunk GA, Shannak K, Haycock JW, Kish SJ: Striatal dopamine nerve terminal markers in human, chronic methamphetamine users. Nat Med 1996;2:699–703.
  32. Sekine Y, Iyo M, Ouchi Y, Matsunaga T, Tsukada H, Okada H, Yoshikawa E, Futatsubashi M, Takei N, Mori N: Methamphetamine-related psychiatric symptoms and reduced brain dopamine transporters studied with PET. Am J Psychiatry 2001;158:1206–1214.
  33. McCann UD, Wong DF, Yokoi F, Villemagne V, Dannals RF, Ricaurte GA: Reduced striatal dopamine transporter density in abstinent methamphetamine and methcathinone users: Evidence from positron emission tomography studies with [11C]WIN-35,428. J Neurosci 1998;18:8417–8422.
  34. Dluzen DE: Neuroprotective effects of estrogen upon the nigrostriatal dopaminergic system. J Neurocytol 2000;29:387–399.
  35. Gao X, Dluzen DE: The effect of testosterone upon methamphetamine neurotoxicity of the nigrostriatal dopaminergic system. Brain Res 2001;892:63–69.


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