title: Enteric Dysfunctions in Experimental Parkinson's Disease: Alterations of Excitatory Cholinergic Neurotransmission Regulating Colonic Motility in Rats.
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.
authors.affiliation: 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 Diseases, "C. Mondino" National Neurologic Institute, Pavia, Italy (F.B., G.L., S.C.); and Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy (R.C.).
authors.forename: Matteo
authors.initials: M
authors.lastname: Fornai
authors.affiliation: 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 Diseases, "C. Mondino" National Neurologic Institute, Pavia, Italy (F.B., G.L., S.C.); and Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy (R.C.).
authors.forename: Carolina
authors.initials: C
authors.lastname: Pellegrini
authors.affiliation: 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 Diseases, "C. Mondino" National Neurologic Institute, Pavia, Italy (F.B., G.L., S.C.); and Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy (R.C.) lucaant@gmail.com.
authors.forename: Luca
authors.initials: L
authors.lastname: Antonioli
authors.affiliation: 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 Diseases, "C. Mondino" National Neurologic Institute, Pavia, Italy (F.B., G.L., S.C.); and Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy (R.C.).
authors.forename: Cristina
authors.initials: C
authors.lastname: Segnani
authors.affiliation: 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 Diseases, "C. Mondino" National Neurologic Institute, Pavia, Italy (F.B., G.L., S.C.); and Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy (R.C.).
authors.forename: Chiara
authors.initials: C
authors.lastname: Ippolito
authors.affiliation: 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 Diseases, "C. Mondino" National Neurologic Institute, Pavia, Italy (F.B., G.L., S.C.); and Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy (R.C.).
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Barocelli
authors.affiliation: 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 Diseases, "C. Mondino" National Neurologic Institute, Pavia, Italy (F.B., G.L., S.C.); and Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy (R.C.).
authors.forename: Vigilio
authors.initials: V
authors.lastname: Ballabeni
authors.affiliation: 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 Diseases, "C. Mondino" National Neurologic Institute, Pavia, Italy (F.B., G.L., S.C.); and Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy (R.C.).
authors.forename: Gaia
authors.initials: G
authors.lastname: Vegezzi
authors.affiliation: 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 Diseases, "C. Mondino" National Neurologic Institute, Pavia, Italy (F.B., G.L., S.C.); and Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy (R.C.).
authors.forename: Zainab
authors.initials: Z
authors.lastname: Al Harraq
authors.affiliation: 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 Diseases, "C. Mondino" National Neurologic Institute, Pavia, Italy (F.B., G.L., S.C.); and Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy (R.C.).
authors.forename: Fabio
authors.initials: F
authors.lastname: Blandini
authors.affiliation: 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 Diseases, "C. Mondino" National Neurologic Institute, Pavia, Italy (F.B., G.L., S.C.); and Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy (R.C.).
authors.forename: Giovanna
authors.initials: G
authors.lastname: Levandis
authors.affiliation: 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 Diseases, "C. Mondino" National Neurologic Institute, Pavia, Italy (F.B., G.L., S.C.); and Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy (R.C.).
authors.forename: Silvia
authors.initials: S
authors.lastname: Cerri
authors.affiliation: 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 Diseases, "C. Mondino" National Neurologic Institute, Pavia, Italy (F.B., G.L., S.C.); and Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy (R.C.).
authors.forename: Corrado
authors.initials: C
authors.lastname: Blandizzi
authors.affiliation: 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 Diseases, "C. Mondino" National Neurologic Institute, Pavia, Italy (F.B., G.L., S.C.); and Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy (R.C.).
authors.forename: Nunzia
authors.initials: N
authors.lastname: Bernardini
authors.affiliation: 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 Diseases, "C. Mondino" National Neurologic Institute, Pavia, Italy (F.B., G.L., S.C.); and Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy (R.C.).
authors.forename: Rocchina
authors.initials: R
authors.lastname: Colucci
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D059329:Cholinergic Neurons / Q000000981:diagnostic imaging / Q000378:metabolism; D003106:Colon / Q000000981:diagnostic imaging* / Q000378:metabolism*; D017615:Enteric Nervous System / Q000000981:diagnostic imaging* / Q000378:metabolism*; D005769:Gastrointestinal Motility / Q000502:physiology*; D008297:Male; D009924:Organ Culture Techniques; D020734:Parkinsonian Disorders / Q000000981:diagnostic imaging*; D011859:Radiography; D051381:Rats; D017207:Rats, Sprague-Dawley; D009435:Synaptic Transmission / Q000502:physiology
chemical_list: D000109:Acetylcholine