title: Restoration of intestinal function in an MPTP model of Parkinson's Disease.
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, Cu(II)(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.
authors.affiliation: The Department of Pathology, The University of Melbourne, Victoria 3010, Australia.
authors.forename: L J
authors.initials: LJ
authors.lastname: Ellett
authors.affiliation: The Department of Pathology, The University of Melbourne, Victoria 3010, Australia.|Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Victoria 3010, Australia.
authors.forename: L W
authors.initials: LW
authors.lastname: Hung
authors.affiliation: The Department of Pathology, The University of Melbourne, Victoria 3010, Australia.
authors.forename: R
authors.initials: R
authors.lastname: Munckton
authors.affiliation: The Department of Pathology, The University of Melbourne, Victoria 3010, Australia.|Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Victoria 3010, Australia.
authors.forename: N A
authors.initials: NA
authors.lastname: Sherratt
authors.affiliation: The Department of Pathology, The University of Melbourne, Victoria 3010, Australia.
authors.forename: J
authors.initials: J
authors.lastname: Culvenor
authors.affiliation: The Department of Pathology, The University of Melbourne, Victoria 3010, Australia.
authors.forename: A
authors.initials: A
authors.lastname: Grubman
authors.affiliation: Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Victoria 3010, Australia.|The Department of Anatomy and Neuroscience, The University of Melbourne, Victoria 3010, Australia.
authors.forename: J B
authors.initials: JB
authors.lastname: Furness
authors.affiliation: The Department of Pathology, The University of Melbourne, Victoria 3010, Australia.
authors.forename: A R
authors.initials: AR
authors.lastname: White
authors.affiliation: Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Victoria 3010, Australia.
authors.forename: D I
authors.initials: DI
authors.lastname: Finkelstein
authors.affiliation: Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Victoria 3010, Australia.|The Department of Pharmacology, The University of Melbourne, Victoria 3010, Australia.|Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Victoria 3010, Australia.
authors.forename: K J
authors.initials: KJ
authors.lastname: Barnham
authors.affiliation: The Department of Pathology, The University of Melbourne, Victoria 3010, Australia.
authors.forename: V A
authors.initials: VA
authors.lastname: Lawson
mesh_terms: D000284:Administration, Oral; D000818:Animals; D003248:Constipation / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D056831:Coordination Complexes; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D003672:Defecation / Q000187:drug effects* / Q000502:physiology; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007274:Injections, Intraperitoneal; D020267:MPTP Poisoning / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D009197:Myenteric Plexus / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009942:Organometallic Compounds / Q000494:pharmacology*; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D013882:Thiosemicarbazones / Q000494:pharmacology*
chemical_list: D056831:Coordination Complexes; D018696:Neuroprotective Agents; D009942:Organometallic Compounds; D013882:Thiosemicarbazones; C089548:copper (II) diacetyl-di(N(4)-methylthiosemicarbazone)