Hostname: page-component-8448b6f56d-42gr6 Total loading time: 0 Render date: 2024-04-23T13:41:13.145Z Has data issue: false hasContentIssue false
  • English
  • Français

Interactions Between MPTP-Induced and Age-Related Neuronal Death in a Murine Model of Parkinson’s Disease

Published online by Cambridge University Press:  18 September 2015

William G. Tatton ,
Carol E. Greenwood ,
Nadine A. Seniuk  and
Paul T. Salo
William G. Tatton*
Affiliation:
Center for Research in Neurodegenerative Diseases (W.G.T., N.A.S.)
Carol E. Greenwood
Affiliation:
Department of Physiology (W.G.T., P.T.S.)
Nadine A. Seniuk
Affiliation:
Department of Psychiatry (W.G.T.)
Paul T. Salo
Affiliation:
Department of Nutritional Sciences (C.E.G.), University of Toronto, Toronto
*
Center for Research in Neurodegenerative Diseases, Tanz Neuroscience Building, 6 Queens Park Crescent West, Toronto, Ontario, Canada M5S 1A8
Rights & Permissions [Opens in a new window]

Abstract:

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

Abiotrophy is hypothesized to explain the onset and time course of deficits in Parkinson’s disease (PD) Abiotrophy includes: 1) exposure to agent(s) causing the death of dopaminergic nigrostriatal neurons (DNSns), 2) gradual death of DNSns with age, 3) summation of 1) and 2) until DNSn numbers fall below a threshold for detectable neurological deficits. Murine DNSn death following methyl-phenyl-tetrahydropyridine (MPTP) exposure occurs according to an exponential relationship while age-related death of DNSns occurs according to a second exponential relationship. Summing the two exponential losses overestimates experimental DNSn death showing a simple abiotrophic model is not sufficient. Aged murine DNSns greatly increase their dopamine synthesis and the density of their striatal axon terminals which may explain the above threshold. Murine DNSns die gradually after MPTP exposure and L-deprenyl treatment rescues MPTP-damaged DNSns by a previously undiscovered action, altering the abiotrophic interactions and possibly explaining the slowed progression of PD found with deprenyl treatment.

Type
Research Article
Information
Canadian Journal of Neurological Sciences , Volume 19 , Issue S1: 3rd Canadian Conference on Neurodegenerative Diseases , February 1992 , pp. 124 - 133
Copyright
Copyright © Canadian Neurological Sciences Federation 1992

References

1.Forno, LS.Pathology of Parkinson’s disease. In: Marsden, CD, Fahn, S, eds. Movement Disorders. London: Butterworth Scientific, 1982:25–40.Google Scholar
2.Hornykiewicz, O.Metabolism of brain dopamine in human parkinsonism: neurochemical and clinical aspects. In: Costa, E, Cote, LJ, Yahr, MD, eds. Biochemistry and Pharmacology of the Basal Ganglia. New York: Raven Press, 1966: 171–185.Google Scholar
3.Duvoisin, RC.The cause of Parkinson’s disease. In: Marsden, CD, Fahn, S, eds. Movement Disorders. London: Butterworth Scientific, 1981:8–24.Google Scholar
4.Tanner, CM.The role of environmental toxins in the etiology of Parkinson’s disease. Trends Neurosci 1989; 12(2): 49–54.CrossRefGoogle ScholarPubMed
5.McGeer, PL, Itagaki, S, Boyes, BE, et al. Reactive microglia are positive for HLA-DR in the substantia nigra of Parkinson’s and Alzheimer’s disease brains. Neurology 1988; 38: 1285–1291.CrossRefGoogle ScholarPubMed
6.Akiyama, H, McGeer, PL.Microglial response to 6-hydroxy-dopamine-induce substantia nigra lesions. Brain Res 1989; 489(2): 247–253.CrossRefGoogle ScholarPubMed
7.Langston, JW, Ballard, P.Parkinsonism induced by l-methyl-4-pheny 1–1, 2, 3, 6 tetrahydropyridine implications for treatment and the pathogenesis of Parkinson’s disease. Symposium on Current Concepts and Controversies in Parkinson’s Disease, Montebello, Quebec, Canada, Oct., 1983.Google Scholar
8.Calne, DB, Langston, JW.Etiology of Parkinson’s disease. Lancet 1983; 2(8365–8366): 1457–1459.CrossRefGoogle Scholar
9.Mann, DMA, Yates, PO, Marcyniuk, B.Monoaminergic neurotransmitter systems in presenile Alzheimer’s disease and in senile dementia of Alzheimer type. Clin Neuropathol 1984; 3: 199–205.Google ScholarPubMed
10.McGeer, PL, McGeer, EG, Suzuki, JS.Aging and extrapyramidal function. Arch Neurol 1977: 34: 33–35.CrossRefGoogle ScholarPubMed
11.McGeer, PL, Itagaki, S, Akiyama, H, et al. Comparison of neuronal loss in Parkinson’s disease and aging. In: Calne, DB, Comi, G, Horowski, R, eds. Parkinsonism and Aging. New York: Plenum, 1989:25–34.Google Scholar
12.Azmitia, EC, Whitaker-Azmitia, PM, Bartus, R.Use of tissue culture models to study neuronal regulatory trophic and toxic factors in the aged brain. Neurobiol Aging 1988; 9: 743–758.CrossRefGoogle ScholarPubMed
13.Gower, WR.Degeneration of nerve cells in the human brain. Lancet 1902; 1: 1003–1007.Google Scholar
14.Martin, WRW, Palmer, MR, Patlak, CS, et al. Nigrostriatal function in humans studied with positron emission tomography. Ann Neurol 1989; 26(4): 535–542.CrossRefGoogle ScholarPubMed
15.Guttman, M, Yong, VW, Kim, SU, et al. Asymptomatic striatal dopamine depletion PET scans in unilateral MPTP monkeys. Synapse (NY) 1988; 2(5): 469–473.CrossRefGoogle ScholarPubMed
16.Burns, BS, Chiueh, CC, Markey, SP, et al. A primate model of parkinsonism selective destruction of dopaminergic neurons in the pars compacta of the substantia nigra by l-methyl-4-phenyl-1, 2, 3, 6 tetrahydropyridine. Proc Natl Acad Sci U.S.A. 1983; 80 (14): 4546–4550.CrossRefGoogle Scholar
17.Chiueh, CC, Burns, RS, Markey, SP, et al. Primate model of parkinsonism selective lesion of nigrostriatal neurons by 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine produces an extrapyramidal syndrome in rhesus monkeys. Symposium on the Pharmacological Features of the Dopaminergic Neurotoxin MPTP 1984; 36(3): 213–218.Google Scholar
18.Damato, RJ, Alexander, GM, Schwartzman, RJ, et al. Evidence for neuromelanin involvement in MPTP-induced neurotoxicity. Nature (Lond) 1987; 327: 324–326.CrossRefGoogle ScholarPubMed
19.Graham, DG.Oxidative pathways from catecholamines in the genesis of neuromelanin and cytotoxic quinones. Mol Pharmacol 1978; 14: 633–643.Google ScholarPubMed
20.Heikkila, RE, Manzino, L, Cabbat, FS, et al. Protection against the dopaminergic neurotoxicity of l-methyl-4-phenyl-1, 2, 5, 6-tetrahydropyridine by monoamine oxidase inhibitors. Nature 1984; 311: 467–469.CrossRefGoogle Scholar
21.Heikkila, RE, Duvoisin, RC, Finberg, JPM, et al. Prevention of 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine-induced neurotoxicity by agn-1133 and agn-1135 selective inhibitors of monoamine oxidase b. Eur J Pharmacol 1985; 116(3): 313–318.CrossRefGoogle Scholar
22.Markey, SP, Johannessen, JN, Chiueh, CC, et al. Intraneuronal generation of a pyridinium metabolite may cause drug-induced parkinsonism. Nature 1984; 311: 465–467.CrossRefGoogle ScholarPubMed
23.Ricuarte, GA, Langston, JW, Delanney, LE, et al. Fate of nigro-striatal neurons in young mature mice given l-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine: a neurochemical and morphological reassessment. Brain Res 1986; 376: 117–124.CrossRefGoogle Scholar
24.Sundstrom, E, Stromberg, I, Tsutsumi, T, et al. Studies on the effect of l-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine MPTP on central catecholamine neurons in C57bl-6 mice: comparison with three other strains of mice. Brain Res 1987; 405(1): 26–38.CrossRefGoogle Scholar
25.Vincent, SR.Histochemical localization of l-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine oxidation in the mouse brain. Neuroscience 1989; 28: 189–199.CrossRefGoogle Scholar
26.Willoughby, J, Glover, V, Sandler, M.Histochemical localization of monoamine oxidase a and b in rat brain. J Neural Transm 1988; 74(1): 29–42.CrossRefGoogle Scholar
27.Westlund, KN, Denney, RM, Rose, RM, et al. Localization of distinct monoamine oxidase a and monoamine oxidase b cell populations in human brainstem. Neuroscience 1988; 25(2): 439–456.CrossRefGoogle ScholarPubMed
28.Westlund, KN, Denney, RM, Kochersperger, LM, et al. Distinct monoamine oxidase a and b populations in primate brain. Science 1985; 230: 181–183.CrossRefGoogle Scholar
29.Ransom, BR, Kunis, DM, Irwin, I, et al. Astrocytes convert the parkinsonism inducing neurotoxin MPTP to its active metabolite MPP+. Neurosci Lett 1987; 75(3): 323–328.CrossRefGoogle ScholarPubMed
30.Brooks, WJ, Jarvis, MF, Wagner, GC.Astrocytes as a primary locus for the conversion MPTP into MPP+. J Neural Transm 1989; 76(1): 1–12.CrossRefGoogle ScholarPubMed
31.Takada, M, Li, ZK, Hattori, T.Astroglial ablation prevents MPTP-induced nigrostriatal neuronal death. Brain Res 1990; 509(1): 55–61.CrossRefGoogle ScholarPubMed
32.Lau, YS, Crampton, JM, Runice, CE, et al. Distribution of tritiated MPTP in mice and their environment. 71st Annual Meeting of the Federation of American Societies for Experimental Biology, Washington, D.C.. U.S.A., March, 1987; 46(3).Google Scholar
33.Lau, YS, Crampton, JM, Wilson, JA.Urinary excretion of MPTP and its primary metabolites in mice. Life Sci 1988; 43(18): 1459–1464.CrossRefGoogle ScholarPubMed
34.Johannessen, JN, Chiueh, CC, Burns, RS, et al. Differences in the metabolism of MPTP in the rodent and primate. Parallel differences in sensitivity to its neurotoxic effects. Life Sci 1985; 36: 219–224.CrossRefGoogle Scholar
35.Yang, SC, Markey, SP, Bankiewicz, KS, et al. Recommended safe practices for using the neurotoxin MPTP in animal experiments. Lab Anim Sci 1988; 38(5): 563–567.Google ScholarPubMed
36.Yang, SC, Johannessen, JN, Markey, SP.Metabolism of carbon-14 MPTP in mouse and monkey implicates MPP–+ and not bound metabolites as the operative neurotoxin. Chem Res Toxicol 1988; 1(4): 228–233.CrossRefGoogle Scholar
37.Forno, LS, Langston, JW, Delanney, LE, et al. Locus ceruleus lesions and eosinophilic inclusions in l-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine-treated monkeys saimiri-sciureus. Ann Neurol 1986; 20(4): 449–455.CrossRefGoogle Scholar
38.Namura, I, Douillet, P, Sun, CJ, et al. MPP (l-methyl-4-phenylpyridine) is a neurotoxin to dopamine-containing norepinephrine-containing and serotonin-containing neurons. Eur J Pharmacol 1987; 136(1): 31–38.CrossRefGoogle Scholar
39.Tanaka, J, Nakamura, H, Honda, S, et al. Neuropathological study on l-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine of the crab-eating monkey. Acta Neuropathol 1988; 75(4): 370–376.CrossRefGoogle Scholar
40.Seniuk, NA, Tatton, WG, Greenwood, CE.Dose-dependent destruction of the coeruleus-cortical and nigral-striatal projections by MPTP. Brain Res 1990; 527: 7–20.CrossRefGoogle ScholarPubMed
41.Javitch, JA, Damato, RJ, Strittmatter, SM, et al. Parkinsonism-inducing neurotoxin n-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine uptake of the metabolite n-methyl-4-phenylpyridine by dopamine neurons explains selective toxicity. Proc Natl Acad Sci U.S.A. 1985; 82(7): 2173–2177.CrossRefGoogle ScholarPubMed
42.Nicklas, WJ, Vyas, I, Heikkila, RE.Inhibition of NADH-linked oxidation in brain mitochondria by l-methyl-4-phenylpyridine a metabolite of the neurotoxin l-methyl-4-phenyl-1, 2, 3, 6-tetrahy-dropyridine. Life Sci 1985; 36(26): 2503–2508.CrossRefGoogle Scholar
43.Ramsay, RR, Singer, TP.Energy-dependent uptake of n-methyl-4-phenylpyridinium the neurotoxic metabolite of l-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine by mitochondria. J Biol Chem 1986; 135(1): 7585–7587.CrossRefGoogle Scholar
44.Ramsay, RR, Salach, JI, Dadgar, J, et al. Inhibition of mitochondrial NADH dehydrogenase by pyridine derivatives and its possible relationship to experimental and idiopathic parkinsonism. Biochem Biophys Res Commun 1986; 261(7): 269–275.CrossRefGoogle Scholar
45.Mizuno, Y, Suzuki, K, Sone, N, et al. Inhibition of ATP synthesis by l-methyI-4-phenylpyridinium (MPP+) in isolated mitochondria from mouse brains. Neurosci Lett 1987; 81: 204–208.CrossRefGoogle ScholarPubMed
46.Mizuno, Y, Suzuki, K, Sone, N, et al. Inhibition of mitochondrial respiration by l-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) in mouse brain in vivo. Neurosci Lett 1988; 91(3): 349–353.Google Scholar
47.Linder, JC, Klemfuss, H, Groves, PM.Acute ultrastructural and behavioral effects of l-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine MPTP in mice. Neurosci Lett 1987; 82(2): 221–226.CrossRefGoogle Scholar
48.Kitt, CA, Cork, LC, Eidelberg, E, et al. Injury of catecholaminergic neurons after acute exposure to MPTP A TH immunocytochemical study in monkey. NY Acad Sci Ann 1987; 495(0): 730–731.CrossRefGoogle Scholar
49.Barron, KV.Axon regeneration and central nervous system regeneration. In: Seil, FJ, ed. Nerve, Organ and Tissue Regeneration. New York: Academic Press, 1986: 3–38.Google Scholar
50.Tatton, WG, Kwan, MM, Verrier, MC, et al. MPTP produces reversible disappearance of tyrosine hydroxylase containing retinal amacrine cells. Brain Res 1990; 527: 21–32.CrossRefGoogle ScholarPubMed
51.Ross, RA, Joh, TH, Reis, DJ.Reversible changes in the accumulation and activities of tyrosine hydroxylase and dopamine-β-hydroxylase in neurons of nucleus locus coeruleus during the retrograde reaction. Brain Res 1975; 92: 57–72.CrossRefGoogle ScholarPubMed
52.Barron, KD, Banerjee, M, Dentinger, MP, et al. Cytological and cytochemical RNA studies on rubral neurons after unilateral rubrospinal tractotomy the impact of GM-1 ganglioside administration. J Neurosci Res 1989; 22(3): 331–337.CrossRefGoogle ScholarPubMed
53.Koo, EH, Hoffman, PN, Price, DL.Levels of neurotransmitter and cytoskeletal protein mRNAs during nerve regeneration in sympathetic ganglia. Brain Res 1988; 449: 361–363.CrossRefGoogle ScholarPubMed
54.Seniuk, NA.Greenwood, CE, Tatton, WG.Recovery of diurnal locomotory activity after MPTP correlates with increased catecholamine synthesis by surviving neurons. Proc Soc for Neurosci 1990; 16: 1048.Google Scholar
55.Tatton, WG, Greenwood, CE.Rescue of dying neurons: a new action for deprenyl in MPTP parkinsonism. J Neurosci Res 1991; 30: 666–672.CrossRefGoogle ScholarPubMed
56.Seniuk, NA.Neuronal Destruction by MPTP: Neurochemical and Behavioural Compensation by Surviving Neurons. Ph.D. Thesis, University of Toronto 1989: 1: 51–73.Google Scholar
57.Tatton, WG, Greenwood, CE, Verrier, MC, et al. Different rates of age-related loss for four murine monoaminergic neuronal populations. Neurobiol Aging 1991; 12(5): 543–556.CrossRefGoogle ScholarPubMed
58.Tatton, WG, Greenwood, CE, Salo, P.et al. Transmitter synthesis increases in substantia nigra neurons in aged mice. Neurosci Letters 1991; 131: 179–182.CrossRefGoogle Scholar
59.Van der Kooy, D, Coscina, DV, Hattori, T.Is there a non-dopaminergic nigrostriatal pathway? Neuroscience 1981; 6(3): 345–357.CrossRefGoogle Scholar
60.Guyenet, PG, Crane, JK.Non-dopaminergic nigrostriatal pathway. Brain Res 1981; 213: 291–305.CrossRefGoogle ScholarPubMed
61.Greenwood, CE, Tatton, WG, Seniuk, NA, et al. Increased dopamine synthesis in aging substantia nigra neurons. Neurobiol Aging 1991; 12(5): 557–565.CrossRefGoogle ScholarPubMed
62.Konigsmark, BW.Methods for the counting of neurons. In: Nauta, WH, Ebesson, SOE, eds. Contemporary Research Methods in Neuroanatomy. New York: Springer Verlag, 1970: 315–380.Google Scholar
63.Parkinson, SG.Datatop: A multicenter controlled clinical trial in early Parkinson’s disease. Arch Neurol 1989; 46(10): 1052–1060.Google Scholar
64.U.S.A. PSG. Effect of deprenyl on the progression of disability in early Parkinson’s disease. N Engl J Med 1989; 321: 1364–1371.CrossRefGoogle Scholar
65.Tetrud, JW, Langston, JW.Deprenyl and the progression of Parkinson’s disease. Reply Science 1990; 249: 303–304.CrossRefGoogle Scholar
66.Tetrud, JW, Langston, JW.The effect of deprenyl (selegiline) on the natural history of Parkinson’s disease. Science 1989; 245: 519–522.CrossRefGoogle ScholarPubMed
67.Langston, JW.In: Jankovic, J, Tolosa, E, eds. Parkinson’s Disease and Movement Disorders. Baltimore-Munich: Urban and Schwarzenberg, 1988: 75–85.Google Scholar
68.Birkmayer, W, Riederer, P, Youdim, MBH, et al. The potentiation of the anti-akinetic effect of L-dopa treatment by an inhibitor of MAO-B, L-deprenyl. J Neural Transm 1975; 36: 303–336.CrossRefGoogle Scholar
69.Song-cheng, Y, Johannessen, JN, Markey, SP.Metabolism of [C14]MPTP in mouse and monkey implicates MPP+, and not bound metabolites, as the operative toxin. Chem Res Toxicol 1988; 1(4): 228–233.Google Scholar
70.Knoll, J.The striatal dopamine dependence of life span in male rats. Longevity study with (-)deprenyl. Mech Ageing Dev 1988; 46(1–3): 237–262.CrossRefGoogle ScholarPubMed
71.Knoll, J.Extension of life span of rats by long term (-)deprenyl treatment. Mt Sinai J Med 1988; 55: 67–74.Google ScholarPubMed
72.Demarest, KT, Azzaro, AJ.The association of type A monoamine oxidase with the nigrostriatal dopamine neuron. In: Singer, T, Korff, RW, Murphy, DL, eds. Monoamine oxidase: Structure, Function and Altered Functions. New York: Academic Press, 1979: 423–430.Google Scholar
73.Bernheimer, H, Birkmayer, W, Hornykiewicz, O, et al. Brain dopamine and the syndromes of Parkinson and Huntington. Clinical, morphological and neurochemical correlations. J Neurol Sci 1973; 20: 415–455.CrossRefGoogle ScholarPubMed
74. Parkinson Study Group. Effect of deprenyl on the progression of disability in early Parkinson’s disease. N Engl J Med. 1989; 321(20): 1364–1371.CrossRefGoogle Scholar
75.Gupta, M, Schwarz, J.Chen, XL, et al. Gangliosides prevent MPTP toxicity in mice – an immunocytochemical study. Brain Res 1990; 527: 330–334.CrossRefGoogle ScholarPubMed
76.Hadjiconstantinou, M, Neff, NH.Treatment with GM1 ganglioside restores striatal dopamine in the l-methyl-4-pheny 1–1, 2, 3, 6-tetrahydropyridine-treated mouse. J Neurochem 1988; 51(4): 1190–1196.CrossRefGoogle Scholar
77.Date, I, Asari, S, Nishimoto, A, et al. Recovery of nigrostriatal and mesolimbic dopaminergic system following administration of ganglioside in MPTP-treated mice. Brain Nerve (Tokyo) 1990; 42(11): 1035–1040.Google ScholarPubMed
78.Cohen, G, Spina, MB.Deprenyl suppresses the oxidant stress associated with increased dopamine turnover. Ann Neurol 1989; 26: 689–690.CrossRefGoogle ScholarPubMed
79.Paterson, IA, Juorio, AV, Boulton, AA.2-Phenylethylamine: a modulator of catecholamine transmission in the mammalian central nervous system? J Neurochem 1990; 55: 1827–1837.CrossRefGoogle ScholarPubMed