Striatal Dopaminergic Denervation and Spine Loss in MPTP-Treated Monkeys

  • Rosa M. Villalba
  • Heyne Lee
  • Dinesh Raju
  • Yoland Smith
Conference paper
Part of the Advances in Behavioral Biology book series (ABBI, volume 58)

Abstract

Dopamine (DA) plays a critical role in regulating spine density on medium-sized spiny neurons (MSNs) in the striatum. Quantitative analysis of Golgi-impregnated MSNs in striatal sections at the level of the anterior commissure (commissural striatum) from MPTP-treated monkeys with complete DA denervation showed a significant reduction in spine density in both the caudate nucleus and putamen compared with that in controls. Similar analysis in partially DA-denervated striata revealed that the loss of spines was tightly correlated with the relative degree of dopamine depletion. Quantitative electron microscopy (EM) analyses showed a significant decrease in the density of both D1-immunolabeled and immunonegative spines in the commissural putamen of MPTP-treated monkeys, suggesting that DA depletion causes a reduction of spines on both direct and indirect pathway MSNs in the striatum of parkinsonian monkeys. Both the degree of striatal dopamine loss and extent of spine degeneration are correlated with low level of calbindin expression in striatal subregions, suggesting an important role of calcium in striatal pathogenesis of Parkinson’s disease. This is further supported by electron microscopic data showing that calbindin-containing spines are less sensitive to degeneration in the caudate nucleus of partially depleted MPTP-treated monkeys. These findings provide strong evidence that striatal spine loss is an early sign of parkinsonism pathogenesis that is tightly correlated with the degree of striatal dopamine denervation and affects both direct and indirect striatofugal pathway neurons predominantly in calbindin-poor striatal subregions of MPTP-treated monkeys.

Keywords

Ethyl Dopamine Paraformaldehyde Glutaraldehyde Biotin 

Notes

Acknowledgments

The authors thank Dr. T. Wichmann for some of the MPTP-treated animals used in this study. This research was supported by NIH grant R01 NS 037948 to Y. Smith and the NIH base grant to the Yerkes National Primate Research Center (RR 00165).

References

  1. Arbuthnott GW, Ingham CA and Wickens JR (2000) Dopamine and synaptic plasticity in the neostriatum. J Anat 196: 587–596.CrossRefPubMedGoogle Scholar
  2. Bamford NS, Robinson S, Palmiter RD, Joyce JA, Moore C and Meshul CK (2004) Dopamine modulates release from corticostriatal terminals. J Neurosci 24: 9541–9552.CrossRefPubMedGoogle Scholar
  3. Bergman H, Wichmann T and DeLong MR (1990) Reversal of experimental parkinsonism by lesions of the subthalamic nucleus. Science 249: 1436–1438.CrossRefPubMedGoogle Scholar
  4. Bernheimer H, Birkmayer W, Hornykiewicz O, Jellinger K and Seitelberger F (1973) Brain dopamine and the syndromes of Parkinson and Huntington. Clinical, morphological and neurochemical correlations. J Neurol Sci 20: 415–455.CrossRefPubMedGoogle Scholar
  5. Bogenpohl J, Pare J-P and Smith Y (2007) Subcellular localization of adenosine A2A receptors in the striatum and globus pallidus of monkey and rat. Ninth Triennial Meeting of the International Basal Ganglia Society, The Netherlands, September 2–6, 2007.Google Scholar
  6. Cheng HW, Rafols JA, Goshgarian HG, Anavi Y, Tong J and McNeill TH (1997) Differential spine loss and regrowth of striatal neurons following multiple forms of deafferentation: a Golgi study. Exp Neurol 147: 287–298.CrossRefPubMedGoogle Scholar
  7. Damier P, Hirsch EC, Agid Y and Graybiel AM (1999) The substantia nigra of the human brain. II. Patterns of loss of dopamine-containing neurons in Parkinson’s disease. Brain 122: 1437–1448.CrossRefPubMedGoogle Scholar
  8. Dauer W and Przedborski S (2003) Parkinson’s disease: mechanisms and models. Neuron 39: 889–909.CrossRefPubMedGoogle Scholar
  9. Day M, Wang Z, Ding J, An X, Ingham CA, Shering AF, Wokosin D, Ilijic E, Sun Z, Sampson AR, Mugnaini E, Deutch AY, Sesack SR, Arbuthnott GW and Surmeier DJ (2006) Selective elimination of glutamatergic synapses on striatopallidal neurons in Parkinson disease models. Nat Neurosci 9: 251–259.CrossRefPubMedGoogle Scholar
  10. Herkenham M, Little MD, Bankiewicz K, Yang SC, Markey SP and Johannessen JN (1991) Selective retention of MPP+ within the monoaminergic systems of the primate brain following MPTP administration: an in vivo autoradiographic study. Neuroscience 40: 133–158.CrossRefPubMedGoogle Scholar
  11. Hersch SM, Ciliax BJ, Gutekunst CA, Rees HD, Heilman CJ, Yung KK, Bolam JP, Ince E, Yi H and Levey AI (1995) Electron microscopic analysis of D1 and D2 dopamine receptor proteins in the dorsal striatum and their synaptic relationships with motor corticostriatal afferents. J Neurosci 15: 5222–5237.PubMedGoogle Scholar
  12. Hornykiewicz O (2001) Chemical neuroanatomy of the basal ganglia - normal and in Parkinson’s disease. J Chem Neuroanat 22: 3–12.CrossRefPubMedGoogle Scholar
  13. Ingham CA, Hood SH and Arbuthnott GW (1989) Spine density on neostriatal neurones changes with 6-hydroxydopamine lesions and with age. Brain Res 503: 334–338.CrossRefPubMedGoogle Scholar
  14. Ingham CA, Hood SH, van Maldegem B, Weenink A and Arbuthnott GW (1993) Morphological changes in the rat neostriatum after unilateral 6-hydroxydopamine injections into the nigrostriatal pathway. Exp Brain Res 93: 17–27.CrossRefPubMedGoogle Scholar
  15. Ingham CA, Hood SH, Taggart P and Arbuthnott GW (1998) Plasticity of synapses in the rat neostriatum after unilateral lesion of the nigrostriatal dopaminergic pathway. J Neurosci 18: 4732–4743.PubMedGoogle Scholar
  16. Iravani MM, Syed E, Jackson MJ, Johnston LC, Smith LA and Jenner P (2005) A modified MPTP treatment regime produces reproducible partial nigrostriatal lesions in common marmosets. Eur J Neurosci 21: 841–854.CrossRefPubMedGoogle Scholar
  17. Kolb B, Gorny G, Li Y, Samaha AN and Robinson TE (2003) Amphetamine or cocaine limits the ability of later experience to promote structural plasticity in the neocortex and nucleus accumbens. Proc Natl Acad Sci USA 100: 10523–10528.CrossRefPubMedGoogle Scholar
  18. Lei W, Jiao Y, Del Mar N and Reiner A (2004) Evidence for differential cortical input to direct pathway versus indirect pathway striatal projection neurons in rats. J Neurosci 24: 8289–8299.CrossRefPubMedGoogle Scholar
  19. Li Y, Kolb B and Robinson TE (2003) The location of persistent amphetamine-induced changes in the density of dendritic spines on medium spiny neurons in the nucleus accumbens and caudate-putamen. Neuropsychopharmacology 28: 1082–1085.CrossRefPubMedGoogle Scholar
  20. Moratalla R, Quinn B, DeLanney LE, Irwin I, Langston JW and Graybiel AM (1992) Differential vulnerability of primate caudate-putamen and striosome-matrix dopamine systems to the neurotoxic effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Proc Natl Acad Sci USA 89: 3859–3863.CrossRefPubMedGoogle Scholar
  21. Norrholm SD, Bibb JA, Nestler EJ, Ouimet CC, Taylor JR and Greengard P (2003) Cocaine-induced proliferation of dendritic spines in nucleus accumbens is dependent on the activity of cyclin-dependent kinase-5. Neuroscience 116: 19–22.CrossRefPubMedGoogle Scholar
  22. Raju DV, Shah DJ, Wright TM, Hall RA and Smith Y (2006) Differential synaptology of vGluT2-containing thalamostriatal afferents between the patch and matrix compartments in rats. J Comp Neurol 499: 231–243.CrossRefPubMedGoogle Scholar
  23. Robinson TE and Kolb B (1999) Alterations in the morphology of dendrites and dendritic spines in the nucleus accumbens and prefrontal cortex following repeated treatment with amphetamine or cocaine. Eur J Neurosci 11: 1598–1604.CrossRefPubMedGoogle Scholar
  24. Schneider JS and Pope-Coleman A (1995) Cognitive deficits precede motor deficits in a slowly progressing model of parkinsonism in the monkey. Neurodegeneration 4: 245–255.CrossRefPubMedGoogle Scholar
  25. Smith Y and Bolam JP (1990) The output neurones and the dopaminergic neurones of the substantia nigra receive a GABA-containing input from the globus pallidus in the rat. J Comp Neurol 296: 47–64.CrossRefPubMedGoogle Scholar
  26. Soares J, Kliem MA, Betarbet R, Greenamyre JT, Yamamoto B and Wichmann T (2004) Role of external pallidal segment in primate parkinsonism: comparison of the effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonism and lesions of the external pallidal segment. J Neurosci 24: 6417–6426.CrossRefPubMedGoogle Scholar
  27. Stephens B, Mueller AJ, Shering AF, Hood SH, Taggart P, Arbuthnott GW, Bell JE, Kilford L, Kingsbury AE, Daniel SE and Ingham CA (2005) Evidence of a breakdown of corticostriatal connections in Parkinson’s disease. Neuroscience 132: 741–754.CrossRefPubMedGoogle Scholar
  28. Stern Y, Tetrud JW, Martin WR, Kutner SJ and Langston JW (1990) Cognitive change following MPTP exposure. Neurology 40: 261–264.PubMedGoogle Scholar
  29. Villalba R, Verrault M and Smith Y (2006) Spine loss in the striatum of MPTP-treated monkeys: a correlation with the degree of striatal dopaminergic denervation. Society for Neuroscience, Atlanta, GA, October 14–18, 2006.Google Scholar
  30. Villalba R, Lee H, Raju D and Smith Y (2007) Dopaminergic denervation and spine loss in the striatum of MPTP-treated monkeys. Ninth Triennial Meeting of the International Basal Ganglia Society, The Netherlands, September 2–6, 2007.Google Scholar
  31. Wichmann T and Soares J (2006) Neuronal firing before and after burst discharges in the monkey basal ganglia is predictably patterned in the normal state and altered in parkinsonism. J Neurophysiol 95: 2120–2133.CrossRefPubMedGoogle Scholar
  32. Wichmann T, Kliem MA and DeLong MR (2001) Antiparkinsonian and behavioral effects of inactivation of the substantia nigra pars reticulata in hemiparkinsonian primates. Exp Neurol 167: 410–424.CrossRefPubMedGoogle Scholar
  33. Wichmann T, Smith Y and Vitek J (2007) Basal ganglia: anatomy and physiology. In: Factor S and Weiner W (eds) Parkinson’s Disease: Diagnosis and Clinical Management. New York: Demos.Google Scholar
  34. Zaja-Milatovic S, Milatovic D, Schantz AM, Zhang J, Montine K, Sami A, Deutch AY and Montine TJ (2005) Dendritic degeneration in neostriatal medium spiny neurons in Parkinson disease. Neurology 64: 545–547.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Rosa M. Villalba
    • 1
  • Heyne Lee
    • 1
  • Dinesh Raju
    • 1
  • Yoland Smith
    • 1
  1. 1.Yerkes National Primate Research CenterEmory UniversityAtlantaUSA

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