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        Contractile dysfunction and nitrergic dysregulation in small intestine of a primate model of Parkinson’s disease : contractile dysfunction in MPTP-treated primate ileum

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        Author
        Coletto, E
        Dolan, John S
        Pritchard, Sara
        Gant, Alex
        Hikima, Atsuko
        Jackson, Michael J
        Benham, Christopher
        Chaudhuri, K. Ray
        Rose, Sarah
        Jenner, Peter
        Iravani, Mahmoud
        Attention
        2299/21411
        Abstract
        Bowel dysfunction is a common non-motor symptom in Parkinson's disease (PD). The main contractile neurotransmitter in the GI tract is acetylcholine (ACh), while nitric oxide (NO) causes the relaxation of smooth muscle in addition to modulating ACh release. The aim of this study was to characterise functional and neurochemical changes in the isolated ileum of the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated marmoset, an established model of PD motor dysfunction. While NO-synthase inhibitor L-NAME concentration dependently augmented the neurogenically-evoked contractions and inhibited the relaxations in normal tissues, it had no effects on the MPTP ileum. Immunohistochemical analyses of the myenteric plexus showed that ChAT-immunoreactivity (-ir) was significantly reduced and the density of the enteric glial cells as shown by SOX-10-ir was increased. However, no change in TH-, 5-HT-, VIP- or nNOS-ir was observed in the MPTP tissues. The enhancement of the neurogenically-evoked contractions and the inhibition of the relaxation phase by L-NAME in the control tissues is in line with NO's direct relaxing effect on smooth muscle and its indirect inhibitory effect on ACh release. The absence of the relaxation and the inefficacy of L-NAME in the MPTP tissues suggests that central dopaminergic loss dopamine may eventually lead to the impairment of NO signal coupling that affects bowel function, and this may be the result of a complex dysregulation at the level of the neuroeffector junction.
        Publication date
        2019-06-10
        Published in
        npj Parkinson's Disease
        Published version
        https://doi.org/10.1038/s41531-019-0081-9
        License
        http://creativecommons.org/licenses/by/4.0/
        Other links
        http://hdl.handle.net/2299/21411
        Relations
        School of Life and Medical Sciences
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