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Enteric Dysfunctions in Experimental Parkinson's Disease: Alterations of Excitatory Cholinergic Neurotransmission Regulating Colonic Motility in Rats.
Fornai, Matteo; Pellegrini, Carolina; Antonioli, Luca; Segnani, Cristina; Ippolito, Chiara; Barocelli, Elisabetta; Ballabeni, Vigilio; Vegezzi, Gaia; Al Harraq, Zainab; Blandini, Fabio; Levandis, Giovanna; Cerri, Silvia; Blandizzi, Corrado; Bernardini, Nunzia; Colucci, Rocchina.
Afiliación
  • Fornai M; Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy (M.F., C.P., L.A., C.S., C.I., C.B., N.B.); Department of Pharmacy, University of Parma, Parma, Italy (E.B., V.B., G.V., Z.A.H.); Laboratory of Functional Neurochemistry, Center for Research in Neurodegenerative Diseas
  • Pellegrini C; Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy (M.F., C.P., L.A., C.S., C.I., C.B., N.B.); Department of Pharmacy, University of Parma, Parma, Italy (E.B., V.B., G.V., Z.A.H.); Laboratory of Functional Neurochemistry, Center for Research in Neurodegenerative Diseas
  • Antonioli L; Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy (M.F., C.P., L.A., C.S., C.I., C.B., N.B.); Department of Pharmacy, University of Parma, Parma, Italy (E.B., V.B., G.V., Z.A.H.); Laboratory of Functional Neurochemistry, Center for Research in Neurodegenerative Diseas
  • Segnani C; Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy (M.F., C.P., L.A., C.S., C.I., C.B., N.B.); Department of Pharmacy, University of Parma, Parma, Italy (E.B., V.B., G.V., Z.A.H.); Laboratory of Functional Neurochemistry, Center for Research in Neurodegenerative Diseas
  • Ippolito C; Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy (M.F., C.P., L.A., C.S., C.I., C.B., N.B.); Department of Pharmacy, University of Parma, Parma, Italy (E.B., V.B., G.V., Z.A.H.); Laboratory of Functional Neurochemistry, Center for Research in Neurodegenerative Diseas
  • Barocelli E; Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy (M.F., C.P., L.A., C.S., C.I., C.B., N.B.); Department of Pharmacy, University of Parma, Parma, Italy (E.B., V.B., G.V., Z.A.H.); Laboratory of Functional Neurochemistry, Center for Research in Neurodegenerative Diseas
  • Ballabeni V; Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy (M.F., C.P., L.A., C.S., C.I., C.B., N.B.); Department of Pharmacy, University of Parma, Parma, Italy (E.B., V.B., G.V., Z.A.H.); Laboratory of Functional Neurochemistry, Center for Research in Neurodegenerative Diseas
  • Vegezzi G; Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy (M.F., C.P., L.A., C.S., C.I., C.B., N.B.); Department of Pharmacy, University of Parma, Parma, Italy (E.B., V.B., G.V., Z.A.H.); Laboratory of Functional Neurochemistry, Center for Research in Neurodegenerative Diseas
  • Al Harraq Z; Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy (M.F., C.P., L.A., C.S., C.I., C.B., N.B.); Department of Pharmacy, University of Parma, Parma, Italy (E.B., V.B., G.V., Z.A.H.); Laboratory of Functional Neurochemistry, Center for Research in Neurodegenerative Diseas
  • Blandini F; Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy (M.F., C.P., L.A., C.S., C.I., C.B., N.B.); Department of Pharmacy, University of Parma, Parma, Italy (E.B., V.B., G.V., Z.A.H.); Laboratory of Functional Neurochemistry, Center for Research in Neurodegenerative Diseas
  • Levandis G; Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy (M.F., C.P., L.A., C.S., C.I., C.B., N.B.); Department of Pharmacy, University of Parma, Parma, Italy (E.B., V.B., G.V., Z.A.H.); Laboratory of Functional Neurochemistry, Center for Research in Neurodegenerative Diseas
  • Cerri S; Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy (M.F., C.P., L.A., C.S., C.I., C.B., N.B.); Department of Pharmacy, University of Parma, Parma, Italy (E.B., V.B., G.V., Z.A.H.); Laboratory of Functional Neurochemistry, Center for Research in Neurodegenerative Diseas
  • Blandizzi C; Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy (M.F., C.P., L.A., C.S., C.I., C.B., N.B.); Department of Pharmacy, University of Parma, Parma, Italy (E.B., V.B., G.V., Z.A.H.); Laboratory of Functional Neurochemistry, Center for Research in Neurodegenerative Diseas
  • Bernardini N; Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy (M.F., C.P., L.A., C.S., C.I., C.B., N.B.); Department of Pharmacy, University of Parma, Parma, Italy (E.B., V.B., G.V., Z.A.H.); Laboratory of Functional Neurochemistry, Center for Research in Neurodegenerative Diseas
  • Colucci R; Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy (M.F., C.P., L.A., C.S., C.I., C.B., N.B.); Department of Pharmacy, University of Parma, Parma, Italy (E.B., V.B., G.V., Z.A.H.); Laboratory of Functional Neurochemistry, Center for Research in Neurodegenerative Diseas
J Pharmacol Exp Ther ; 356(2): 434-44, 2016 Feb.
Article en En | MEDLINE | ID: mdl-26582732
ABSTRACT
Parkinson's disease is frequently associated with gastrointestinal symptoms, mostly represented by constipation and defecatory dysfunctions. This study examined the impact of central dopaminergic denervation, induced by injection of 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle, on distal colonic excitatory cholinergic neuromotor activity in rats. Animals were euthanized 4 and 8 weeks after 6-OHDA injection. In vivo colonic transit was evaluated by radiologic assay. Electrically induced and carbachol-induced cholinergic contractions were recorded in vitro from longitudinal and circular muscle colonic preparations, whereas acetylcholine levels were assayed in the incubation media. Choline acetyltransferase (ChAT), HuC/D (pan-neuronal marker), muscarinic M2 and M3 receptors were assessed by immunohistochemistry or western blot assay. As compared with control rats, at week 4, 6-OHDA-treated animals displayed the following changes decreased in vivo colonic transit rate, impaired electrically evoked neurogenic cholinergic contractions, enhanced carbachol-induced contractions, decreased basal and electrically stimulated acetylcholine release from colonic tissues, decreased ChAT immunopositivity in the neuromuscular layer, unchanged density of HuC/D immunoreactive myenteric neurons, and increased expression of colonic muscarinic M2 and M3 receptors. The majority of such alterations were also detected at week 8 post 6-OHDA injection. These findings indicate that central nigrostriatal dopaminergic denervation is associated with an impaired excitatory neurotransmission characterized by a loss of myenteric neuronal ChAT positivity and decrease in acetylcholine release, resulting in a dysregulated smooth muscle motor activity, which likely contributes to the concomitant decrease in colonic transit rate.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Acetilcolina / Colon / Sistema Nervioso Entérico / Trastornos Parkinsonianos / Motilidad Gastrointestinal Tipo de estudio: Diagnostic_studies Límite: Animals Idioma: En Revista: J Pharmacol Exp Ther Año: 2016 Tipo del documento: Article
Texto completo
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Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Acetilcolina / Colon / Sistema Nervioso Entérico / Trastornos Parkinsonianos / Motilidad Gastrointestinal Tipo de estudio: Diagnostic_studies Límite: Animals Idioma: En Revista: J Pharmacol Exp Ther Año: 2016 Tipo del documento: Article