mptp poisoning

Summary

Summary: A condition caused by the neurotoxin MPTP which causes selective destruction of nigrostriatal dopaminergic neurons. Clinical features include irreversible parkinsonian signs including rigidity and bradykinesia (PARKINSON DISEASE, SECONDARY). MPTP toxicity is also used as an animal model for the study of PARKINSON DISEASE. (Adams et al., Principles of Neurology, 6th ed, p1072; Neurology 1986 Feb;36(2):250-8)

Top Publications

  1. Yasuda T, Hayakawa H, Nihira T, Ren Y, Nakata Y, Nagai M, et al. Parkin-mediated protection of dopaminergic neurons in a chronic MPTP-minipump mouse model of Parkinson disease. J Neuropathol Exp Neurol. 2011;70:686-97 pubmed publisher
    ..On the other hand, upregulation of p53 and mitochondrial alterations induced by chronic MPTP administration were barely suppressed by parkin. These results suggest that the neuroprotective actions of parkin may be impaired in severe PD...
  2. Richardson J, Caudle W, Wang M, Dean E, Pennell K, Miller G. Developmental heptachlor exposure increases susceptibility of dopamine neurons to N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)in a gender-specific manner. Neurotoxicology. 2008;29:855-63 pubmed publisher
    ..These data suggest that developmental heptachlor exposure causes long-term alterations of the dopamine system thereby rendering it more susceptible to dopaminergic damage in adulthood...
  3. Pothakos K, Kurz M, Lau Y. Restorative effect of endurance exercise on behavioral deficits in the chronic mouse model of Parkinson's disease with severe neurodegeneration. BMC Neurosci. 2009;10:6 pubmed publisher
    ..In this research with the chronic MPD, we first conducted a series of behavioral tests and then investigated the impact of endurance exercise on the identified Parkinsonian behavioral deficits...
  4. Luchtman D, Shao D, Song C. Behavior, neurotransmitters and inflammation in three regimens of the MPTP mouse model of Parkinson's disease. Physiol Behav. 2009;98:130-8 pubmed publisher
    ..The study also provided additional evidence for the validity of the relatively new chronic MPTP/probenecid model. In all, the results suggested that dosing regimens should be carefully pre-considered...
  5. Vroon A, Drukarch B, Bol J, Cras P, Brevé J, Allan S, et al. Neuroinflammation in Parkinson's patients and MPTP-treated mice is not restricted to the nigrostriatal system: microgliosis and differential expression of interleukin-1 receptors in the olfactory bulb. Exp Gerontol. 2007;42:762-71 pubmed
    ..We suggest that differential regulation of IL-1 signaling can serve as an important mechanism to modulate neuroinflammatory activity after MPTP treatment and possibly during PD...
  6. Anantharam V, Kaul S, Song C, Kanthasamy A, Kanthasamy A. Pharmacological inhibition of neuronal NADPH oxidase protects against 1-methyl-4-phenylpyridinium (MPP+)-induced oxidative stress and apoptosis in mesencephalic dopaminergic neuronal cells. Neurotoxicology. 2007;28:988-97 pubmed
    ..This study supports a critical role of NADPH oxidase in the oxidative damage in PD; targeting this enzyme may lead to novel therapies for PD...
  7. Muroyama A, Kobayashi S, Mitsumoto Y. Loss of striatal dopaminergic terminals during the early stage in response to MPTP injection in C57BL/6 mice. Neurosci Res. 2011;69:352-5 pubmed publisher
    ..These results suggest that the isolated DAergic synaptosomes can be useful to identify mechanisms of loss of the nerve terminals...
  8. Tsai S, Chao C, Yin M. Preventive and therapeutic effects of caffeic acid against inflammatory injury in striatum of MPTP-treated mice. Eur J Pharmacol. 2011;670:441-7 pubmed publisher
    ..05). These results suggest that caffeic acid is a potent neuroprotective agent against the development of Parkinson's disease. ..
  9. Moon M, Kim H, Hwang L, Seo J, Kim S, Hwang S, et al. Neuroprotective effect of ghrelin in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson's disease by blocking microglial activation. Neurotox Res. 2009;15:332-47 pubmed publisher

More Information

Publications62

  1. Hu X, Zhang D, Pang H, Caudle W, Li Y, Gao H, et al. Macrophage antigen complex-1 mediates reactive microgliosis and progressive dopaminergic neurodegeneration in the MPTP model of Parkinson's disease. J Immunol. 2008;181:7194-204 pubmed
  2. He X, Yamauchi H, Uetsuka K, Nakayama H. Neurotoxicity of MPTP to migrating neuroblasts: studies in acute and subacute mouse models of Parkinson's disease. Neurotoxicology. 2008;29:413-20 pubmed publisher
    ..Furthermore, our data suggests that the death and subsequent loss of migrating neuroblasts in the acute or subacute model probably lead to a decreased potential for neurogenesis to some extent...
  3. Bousquet M, Saint Pierre M, Julien C, Salem N, Cicchetti F, Calon F. Beneficial effects of dietary omega-3 polyunsaturated fatty acid on toxin-induced neuronal degeneration in an animal model of Parkinson's disease. FASEB J. 2008;22:1213-25 pubmed
    ..05 vs. MPTP mice on control diet) in the striatum. Taken together, these data suggest that a high n-3 PUFA dietary intake exerts neuroprotective actions in an animal model of Parkinsonism...
  4. Kurz M, Pothakos K, Jamaluddin S, Scott Pandorf M, Arellano C, Lau Y. A chronic mouse model of Parkinson's disease has a reduced gait pattern certainty. Neurosci Lett. 2007;429:39-42 pubmed
    ..Additionally, our results imply that disorder of the basal ganglia results in less certainty in modulating the descending motor command that controls the gait pattern...
  5. Wang H, Pan Y, Xue B, Wang X, Zhao F, Jia J, et al. The antioxidative effect of electro-acupuncture in a mouse model of Parkinson's disease. PLoS ONE. 2011;6:e19790 pubmed publisher
  6. Chen P, Vargas M, Pani A, Smeyne R, Johnson D, Kan Y, et al. Nrf2-mediated neuroprotection in the MPTP mouse model of Parkinson's disease: Critical role for the astrocyte. Proc Natl Acad Sci U S A. 2009;106:2933-8 pubmed publisher
  7. Reynolds A, Banerjee R, Liu J, Gendelman H, Mosley R. Neuroprotective activities of CD4+CD25+ regulatory T cells in an animal model of Parkinson's disease. J Leukoc Biol. 2007;82:1083-94 pubmed
    ..This neuroprotection was achieved through modulation of microglial oxidative stress and inflammation. As Tregs can be modulated in vivo, these data strongly support the use of such immunomodulatory strategies to treat PD...
  8. Ookubo M, Yokoyama H, Kato H, Araki T. Gender differences on MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) neurotoxicity in C57BL/6 mice. Mol Cell Endocrinol. 2009;311:62-8 pubmed publisher
    ..The gender difference may be due to the decrease of DAT expression caused by MPTP. Thus our findings provide further valuable information for the pathogenesis of PD...
  9. Gibrat C, Saint Pierre M, Bousquet M, Levesque D, Rouillard C, Cicchetti F. Differences between subacute and chronic MPTP mice models: investigation of dopaminergic neuronal degeneration and alpha-synuclein inclusions. J Neurochem. 2009;109:1469-82 pubmed publisher
    ..Overall, we found that the 14-day chronic MPTP i.p. infusion reproduces more accurately the pathological characteristics of early stage Parkinson's disease...
  10. Luo D, Zhang Q, Wang H, Cui Y, Sun Z, Yang J, et al. Fucoidan protects against dopaminergic neuron death in vivo and in vitro. Eur J Pharmacol. 2009;617:33-40 pubmed publisher
    ..Taken together, these findings suggest that fucoidan has protective effect in MPTP-induced neurotoxicity in this model of Parkinson's disease via its antioxidative activity...
  11. Khan M, Hoda M, Ishrat T, Ahmad A, Khan M, Khuwaja G, et al. Amelioration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced behavioural dysfunction and oxidative stress by Pycnogenol in mouse model of Parkinson's disease. Behav Pharmacol. 2010;21:563-71 pubmed publisher
    ..Thus, PYC may be used to prevent or reduce the deterioration caused by free radicals, thereby preventing subsequent behavioural and biochemical changes that occur in Parkinsonian mice...
  12. Sager T, Kirchhoff J, Mørk A, van Beek J, Thirstrup K, Didriksen M, et al. Nest building performance following MPTP toxicity in mice. Behav Brain Res. 2010;208:444-9 pubmed publisher
    ..However, after 28 days the change in behavior was no longer detected, which may reflect the plasticity of the tyrosine hydroxylase positive neurons in the dorsolateral part of striatum...
  13. Takagi S, Hayakawa N, Kimoto H, Kato H, Araki T. Damage to oligodendrocytes in the striatum after MPTP neurotoxicity in mice. J Neural Transm (Vienna). 2007;114:1553-7 pubmed
    ..These results demonstrate that oligodendrocytes in the striatum are damaged after MPTP treatment. Thus our present findings provide valuable information for the pathogenesis of Parkinson's disease...
  14. Viaro R, Sanchez Pernaute R, Marti M, Trapella C, Isacson O, Morari M. Nociceptin/orphanin FQ receptor blockade attenuates MPTP-induced parkinsonism. Neurobiol Dis. 2008;30:430-8 pubmed publisher
    ..We conclude that endogenous N/OFQ modulates motor activity in mice and nonhuman primates and contributes to parkinsonian symptoms in MPTP-treated animals. NOP receptor antagonists may represent a novel approach to Parkinson's disease...
  15. Smith B, Goldberg N, Meshul C. Effects of treadmill exercise on behavioral recovery and neural changes in the substantia nigra and striatum of the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned mouse. Brain Res. 2011;1386:70-80 pubmed publisher
  16. Drouin Ouellet J, Gibrat C, Bousquet M, Calon F, Kriz J, Cicchetti F. The role of the MYD88-dependent pathway in MPTP-induced brain dopaminergic degeneration. J Neuroinflammation. 2011;8:137 pubmed publisher
    ..These include tumor necrosis factor, prostaglandins and oxidative-related stress components. However, the role of innate immunity has not been established in PD...
  17. Liu K, Shi N, Sun Y, Zhang T, Sun X. Therapeutic effects of rapamycin on MPTP-induced Parkinsonism in mice. Neurochem Res. 2013;38:201-7 pubmed publisher
    ..Thus, further investigation into the effectiveness of rapamycin administration in the treatment of PD is warranted...
  18. Shaw V, Spana S, Ashkan K, Benabid A, Stone J, Baker G, et al. Neuroprotection of midbrain dopaminergic cells in MPTP-treated mice after near-infrared light treatment. J Comp Neurol. 2010;518:25-40 pubmed publisher
    ..In summary, our results indicate that NIr light treatment offers neuroprotection against MPTP toxicity for dopaminergic cells in the SNc, but not in the ZI-Hyp...
  19. Reynolds A, Stone D, Hutter J, Benner E, Mosley R, Gendelman H. Regulatory T cells attenuate Th17 cell-mediated nigrostriatal dopaminergic neurodegeneration in a model of Parkinson's disease. J Immunol. 2010;184:2261-71 pubmed publisher
    ..Taken together, these results demonstrate Treg control of N-alpha-syn-induced neurodestructive immunity and, as such, provide a sound rationale for future Parkinson's disease immunization strategies...
  20. Cartelli D, Ronchi C, Maggioni M, Rodighiero S, Giavini E, Cappelletti G. Microtubule dysfunction precedes transport impairment and mitochondria damage in MPP+ -induced neurodegeneration. J Neurochem. 2010;115:247-58 pubmed publisher
  21. Barbiero J, Santiago R, Lima M, Ariza D, Morais L, Andreatini R, et al. Acute but not chronic administration of pioglitazone promoted behavioral and neurochemical protective effects in the MPTP model of Parkinson's disease. Behav Brain Res. 2011;216:186-92 pubmed publisher
    ..Nevertheless, we failed to demonstrate that pioglitazone administration improved performance on a dopamine-related cognitive task after MPTP...
  22. Peng J, Andersen J. Mutant ?-synuclein and aging reduce neurogenesis in the acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of Parkinson's disease. Aging Cell. 2011;10:255-62 pubmed publisher
    ..This could provide a novel therapeutic target for chronic brain repair in this condition...
  23. Chung Y, Kim S, Park J, Chung E, Park K, Won S, et al. Fluoxetine prevents MPTP-induced loss of dopaminergic neurons by inhibiting microglial activation. Neuropharmacology. 2011;60:963-74 pubmed publisher
  24. Hutter Saunders J, Gendelman H, Mosley R. Murine motor and behavior functional evaluations for acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intoxication. J Neuroimmune Pharmacol. 2012;7:279-88 pubmed publisher
    ..We conclude that the rotarod and open field tests provide reliable measures of motor function for MPTP-intoxicated mice...
  25. Ros Bernal F, Hunot S, Herrero M, Parnadeau S, Corvol J, Lu L, et al. Microglial glucocorticoid receptors play a pivotal role in regulating dopaminergic neurodegeneration in parkinsonism. Proc Natl Acad Sci U S A. 2011;108:6632-7 pubmed publisher
    ..Together, our data indicate that GR is important in curtailing microglial reactivity, and its deregulation in PD could lead to sustained inflammation-mediated DN injury...
  26. Karunakaran S, Saeed U, Mishra M, Valli R, Joshi S, Meka D, et al. Selective activation of p38 mitogen-activated protein kinase in dopaminergic neurons of substantia nigra leads to nuclear translocation of p53 in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated mice. J Neurosci. 2008;28:12500-9 pubmed publisher
    ..Selective inhibitors of p38 may therefore, help preserve the surviving neurons in PD and slow down the disease progression...
  27. Yang Y, Zhang S, Ding J, Zhou F, Hu G. Iptakalim protects against MPP+-induced degeneration of dopaminergic neurons in association with astrocyte activation. Int J Neuropsychopharmacol. 2009;12:317-27 pubmed publisher
    ..Together, these findings suggest that Ipt may protect against MPP+-induced degeneration of dopaminergic neurons by inhibiting astrocyte activation and subsequent release of pro-inflammatory factors...
  28. Nagel F, Bahr M, Dietz G. Tyrosine hydroxylase-positive amacrine interneurons in the mouse retina are resistant against the application of various parkinsonian toxins. Brain Res Bull. 2009;79:303-9 pubmed publisher
    ..No loss of TH(+) amacrine cells in the retina was observed, suggesting different properties and less vulnerability of amacrine neurons compared with DA neurons in the midbrain...
  29. Cannon J, Greenamyre J. Neurotoxic in vivo models of Parkinson's disease recent advances. Prog Brain Res. 2010;184:17-33 pubmed publisher
    ..The roles these new advances in modeling may have in future PD research are examined in this chapter...
  30. Kim S, Moon W, Chae Y, Kim Y, Lee H, Park H. The effect of electroaucpuncture for 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced proteomic changes in the mouse striatum. J Physiol Sci. 2010;60:27-34 pubmed publisher
    ..These proteins are likely related to cellular metabolism. Altogether, we propose that the EA may exert neuroprotective effects in mice striatum through reducing MPTP-induced toxicity such as oxidative stress...
  31. Zhao F, Fan X, Grondin R, Edwards R, Forman E, Moorehead J, et al. Improved methods for electroacupuncture and electromyographic recordings in normal and parkinsonian rhesus monkeys. J Neurosci Methods. 2010;192:199-206 pubmed publisher
    ..The results also indicate that animals, especially those with parkinsonian-like symptoms, could benefit from long-term EA stimulations...
  32. Antzoulatos E, Jakowec M, Petzinger G, Wood R. Sex differences in motor behavior in the MPTP mouse model of Parkinson's disease. Pharmacol Biochem Behav. 2010;95:466-72 pubmed publisher
    ..In gonadectomized mice, this sex difference is reversed...
  33. Faherty C, Raviie Shepherd K, Herasimtschuk A, Smeyne R. Environmental enrichment in adulthood eliminates neuronal death in experimental Parkinsonism. Brain Res Mol Brain Res. 2005;134:170-9 pubmed
    ..This non-pharmacological approach presents significant implications for the prevention and/or treatment of PD...
  34. Bergman H, Deuschl G. Pathophysiology of Parkinson's disease: from clinical neurology to basic neuroscience and back. Mov Disord. 2002;17 Suppl 3:S28-40 pubmed
  35. Feng Z, Wang T, Li D, Fung P, Wilson B, Liu B, et al. Cyclooxygenase-2-deficient mice are resistant to 1-methyl-4-phenyl1, 2, 3, 6-tetrahydropyridine-induced damage of dopaminergic neurons in the substantia nigra. Neurosci Lett. 2002;329:354-8 pubmed
    ..The results of this study indicate an important role of COX-2 in MPTP-induced neuronal degeneration and suggest the possibility that manipulation of the COX-2 could be an important target for therapeutic interventions in PD...
  36. Stephenson D, Meglasson M, Connell M, Childs M, Hajos Korcsok E, Emborg M. The effects of a selective dopamine D2 receptor agonist on behavioral and pathological outcome in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated squirrel monkeys. J Pharmacol Exp Ther. 2005;314:1257-66 pubmed
    ..These results suggest that sumanirole can exert antiparkinsonian effects similar to L-DOPA without the behavioral and morphological consequences of the latter...
  37. Himeda T, Watanabe Y, Tounai H, Hayakawa N, Kato H, Araki T. Time dependent alterations of co-localization of S100beta and GFAP in the MPTP-treated mice. J Neural Transm (Vienna). 2006;113:1887-94 pubmed
    ..These results suggest that the modulation of astrocytic activation may offer a novel therapeutic strategy of Parkinson's disease...
  38. Shan X, Chi L, Bishop M, Luo C, Lien L, Zhang Z, et al. Enhanced de novo neurogenesis and dopaminergic neurogenesis in the substantia nigra of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinson's disease-like mice. Stem Cells. 2006;24:1280-7 pubmed
    ..The increased NPCs in the MPTP-lesioned mice further suggest that experimental approaches to promote de novo neurogenesis may provide an effective therapy for PD by functional replacement of degenerated DA neurons...
  39. Sriram K, Matheson J, Benkovic S, Miller D, Luster M, O Callaghan J. Deficiency of TNF receptors suppresses microglial activation and alters the susceptibility of brain regions to MPTP-induced neurotoxicity: role of TNF-alpha. FASEB J. 2006;20:670-82 pubmed
    ..Taken together, our results are indicative of a region-specific and dual role for TNF-alpha in the brain: a promoter of neurodegeneration in striatum and a protector against neurodegeneration in hippocampus...
  40. Hasbani D, Perez F, Palmiter R, O Malley K. Dopamine depletion does not protect against acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine toxicity in vivo. J Neurosci. 2005;25:9428-33 pubmed
    ..These results suggest that DA does not contribute to acute MPTP toxicity in vivo...
  41. Zhao C, Ling Z, Newman M, Bhatia A, Carvey P. TNF-alpha knockout and minocycline treatment attenuates blood-brain barrier leakage in MPTP-treated mice. Neurobiol Dis. 2007;26:36-46 pubmed
  42. Robertson D, Schmidt O, Ninkina N, Jones P, Sharkey J, Buchman V. Developmental loss and resistance to MPTP toxicity of dopaminergic neurones in substantia nigra pars compacta of gamma-synuclein, alpha-synuclein and double alpha/gamma-synuclein null mutant mice. J Neurochem. 2004;89:1126-36 pubmed
  43. Schlüter O, Fornai F, Alessandri M, Takamori S, Geppert M, Jahn R, et al. Role of alpha-synuclein in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonism in mice. Neuroscience. 2003;118:985-1002 pubmed
  44. Schmidt N, Ferger B. Neurochemical findings in the MPTP model of Parkinson's disease. J Neural Transm (Vienna). 2001;108:1263-82 pubmed
    ..In this review we focus on the MPTP mouse model which is easy practicable and widely used in neuroscience research and draw comparisons to the human pathology in PD...
  45. Karunakaran S, Diwakar L, Saeed U, Agarwal V, Ramakrishnan S, Iyengar S, et al. Activation of apoptosis signal regulating kinase 1 (ASK1) and translocation of death-associated protein, Daxx, in substantia nigra pars compacta in a mouse model of Parkinson's disease: protection by alpha-lipoic acid. FASEB J. 2007;21:2226-36 pubmed
  46. Sriram K, Matheson J, Benkovic S, Miller D, Luster M, O Callaghan J. Mice deficient in TNF receptors are protected against dopaminergic neurotoxicity: implications for Parkinson's disease. FASEB J. 2002;16:1474-6 pubmed
    ..Moreover, because TNF-alpha is synthesized predominantly by microglia and astrocytes, our findings implicate the participation of glial cells in MPTP-induced neurotoxicity. Similar mechanisms may underlie the etiopathogenesis of PD...
  47. Tillerson J, Miller G. Grid performance test to measure behavioral impairment in the MPTP-treated-mouse model of parkinsonism. J Neurosci Methods. 2003;123:189-200 pubmed
    ..Employment of this test will allow for more efficacious use of mice in PD research, as well as provide more sensitive measures of behavioral improvement following potential therapeutic or neuroprotective interventions...
  48. Przedborski S, Tieu K, Perier C, Vila M. MPTP as a mitochondrial neurotoxic model of Parkinson's disease. J Bioenerg Biomembr. 2004;36:375-9 pubmed
    ..How mitochondria are affected by MPTP and how their defect contributes to the demise of dopaminergic neurons in this model of PD are discussed in this review...
  49. Shimoji M, Zhang L, Mandir A, Dawson V, Dawson T. Absence of inclusion body formation in the MPTP mouse model of Parkinson's disease. Brain Res Mol Brain Res. 2005;134:103-8 pubmed
    ..Our data showed that although there is a significant decrease in DA content and its metabolites and tyrosine hydroxylase immunoreactivity, there is no inclusion body formation following the various MPTP treatment regimens...
  50. McGeer P, Schwab C, Parent A, Doudet D. Presence of reactive microglia in monkey substantia nigra years after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine administration. Ann Neurol. 2003;54:599-604 pubmed
    ..The mechanism is unknown but could have important implications regarding the cause of Parkinson's disease and possible approaches to therapy...
  51. Dong Z, Ferger B, Feldon J, Bueler H. Overexpression of Parkinson's disease-associated alpha-synucleinA53T by recombinant adeno-associated virus in mice does not increase the vulnerability of dopaminergic neurons to MPTP. J Neurobiol. 2002;53:1-10 pubmed
  52. Dehmer T, Heneka M, Sastre M, Dichgans J, Schulz J. Protection by pioglitazone in the MPTP model of Parkinson's disease correlates with I kappa B alpha induction and block of NF kappa B and iNOS activation. J Neurochem. 2004;88:494-501 pubmed
    ..In conclusion, treatment with pioglitazone may offer a treatment opportunity in PD to slow the progression of disease that is mediated by inflammation...
  53. Battaglia G, Busceti C, Molinaro G, Biagioni F, Traficante A, Nicoletti F, et al. Pharmacological activation of mGlu4 metabotropic glutamate receptors reduces nigrostriatal degeneration in mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. J Neurosci. 2006;26:7222-9 pubmed
    ..These data support the view that mGlu4 receptors are potential targets for the experimental treatment of parkinsonism...