Restoration of intestinal function in an MPTP model of Parkinson's Disease

L. J. Ellett, L. W. Hung, R. Munckton, N. A. Sherratt, J. Culvenor, A. Grubman, J. B. Furness, A. R. White, D. I. Finkelstein, K. J. Barnham, V. A. Lawson

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Patients with Parkinson's disease often experience non-motor symptoms including constipation, which manifest prior to the onset of debilitating motor signs. Understanding the causes of these non-motor deficits and developing disease modifying therapeutic strategies has the potential to prevent disease progression. Specific neuronal subpopulations were reduced within the myenteric plexus of mice 21 days after intoxication by the intraperitoneal administration of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) and was associated with a reduction in stool frequency, indicative of intestinal dysfunction. Oral administration of the divalent copper complex, CuII (atsm), which has been shown to be neuroprotective and restore motor performance to MPTP lesioned mice, improved stool frequency and was correlated with restoration of neuronal subpopulations in the myenteric plexus of MPTP lesioned mice. Restoration of intestinal function was associated with reduced enteric glial cell reactivity and reduction of markers of inflammation. Therapeutics that have been shown to be neuroprotective in the central nervous system, such as Cu II (atsm), therefore also provide symptom relief and are disease modifying in the intestinal tract, suggesting that there is a common cause of Parkinson's disease pathogenesis in the enteric nervous system and central nervous system.
Original languageEnglish
Article number30269
Number of pages11
JournalScientific Reports
Volume6
DOIs
Publication statusPublished - 29 Jul 2016
Externally publishedYes

Cite this

Ellett, L. J., Hung, L. W., Munckton, R., Sherratt, N. A., Culvenor, J., Grubman, A., ... Lawson, V. A. (2016). Restoration of intestinal function in an MPTP model of Parkinson's Disease. Scientific Reports, 6, [30269]. https://doi.org/10.1038/srep30269
Ellett, L. J. ; Hung, L. W. ; Munckton, R. ; Sherratt, N. A. ; Culvenor, J. ; Grubman, A. ; Furness, J. B. ; White, A. R. ; Finkelstein, D. I. ; Barnham, K. J. ; Lawson, V. A. / Restoration of intestinal function in an MPTP model of Parkinson's Disease. In: Scientific Reports. 2016 ; Vol. 6.
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abstract = "Patients with Parkinson's disease often experience non-motor symptoms including constipation, which manifest prior to the onset of debilitating motor signs. Understanding the causes of these non-motor deficits and developing disease modifying therapeutic strategies has the potential to prevent disease progression. Specific neuronal subpopulations were reduced within the myenteric plexus of mice 21 days after intoxication by the intraperitoneal administration of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) and was associated with a reduction in stool frequency, indicative of intestinal dysfunction. Oral administration of the divalent copper complex, CuII (atsm), which has been shown to be neuroprotective and restore motor performance to MPTP lesioned mice, improved stool frequency and was correlated with restoration of neuronal subpopulations in the myenteric plexus of MPTP lesioned mice. Restoration of intestinal function was associated with reduced enteric glial cell reactivity and reduction of markers of inflammation. Therapeutics that have been shown to be neuroprotective in the central nervous system, such as Cu II (atsm), therefore also provide symptom relief and are disease modifying in the intestinal tract, suggesting that there is a common cause of Parkinson's disease pathogenesis in the enteric nervous system and central nervous system.",
author = "Ellett, {L. J.} and Hung, {L. W.} and R. Munckton and Sherratt, {N. A.} and J. Culvenor and A. Grubman and Furness, {J. B.} and White, {A. R.} and Finkelstein, {D. I.} and Barnham, {K. J.} and Lawson, {V. A.}",
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Ellett, LJ, Hung, LW, Munckton, R, Sherratt, NA, Culvenor, J, Grubman, A, Furness, JB, White, AR, Finkelstein, DI, Barnham, KJ & Lawson, VA 2016, 'Restoration of intestinal function in an MPTP model of Parkinson's Disease' Scientific Reports, vol. 6, 30269. https://doi.org/10.1038/srep30269

Restoration of intestinal function in an MPTP model of Parkinson's Disease. / Ellett, L. J.; Hung, L. W.; Munckton, R.; Sherratt, N. A.; Culvenor, J.; Grubman, A.; Furness, J. B.; White, A. R.; Finkelstein, D. I.; Barnham, K. J.; Lawson, V. A.

In: Scientific Reports, Vol. 6, 30269, 29.07.2016.

Research output: Contribution to journalArticleResearchpeer-review

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