Parkinson's disease (PD) 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 radiological assay. Electrically and carbachol-induced cholinergic contractions were recorded in vitro from longitudinal and circular muscle colonic preparations, while acetylcholine levels were assayed in their incubation media. Choline acetyltransferase (ChAT), HuC/D (pan-neuronal marker), muscarinic M2 and M3 receptors. 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; increased expression of colonic muscarinic M2 and M3 receptors. The majority of such alterations were detected also 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.

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; Harraq, Zainab al; Blandini, Fabio; Levandis, Giovanna; Cerri, Silvia; Blandizzi, Corrado; Bernardini, Nunzia; Colucci, Rocchina. - In: THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS. - ISSN 1521-0103. - 356:2(2016), pp. 434-444. [10.1124/jpet.115.228510]

Enteric dysfunctions in experimental Parkinson's disease: alterations of excitatory cholinergic neurotransmission regulating colonic motility in rats

BAROCELLI, Elisabetta;BALLABENI, Vigilio;
2016-01-01

Abstract

Parkinson's disease (PD) 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 radiological assay. Electrically and carbachol-induced cholinergic contractions were recorded in vitro from longitudinal and circular muscle colonic preparations, while acetylcholine levels were assayed in their incubation media. Choline acetyltransferase (ChAT), HuC/D (pan-neuronal marker), muscarinic M2 and M3 receptors. 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; increased expression of colonic muscarinic M2 and M3 receptors. The majority of such alterations were detected also 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.
2016
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; Harraq, Zainab al; Blandini, Fabio; Levandis, Giovanna; Cerri, Silvia; Blandizzi, Corrado; Bernardini, Nunzia; Colucci, Rocchina. - In: THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS. - ISSN 1521-0103. - 356:2(2016), pp. 434-444. [10.1124/jpet.115.228510]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11381/2797588
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