Gastric motor dysfunctions in Parkinson's disease: Current pre-clinical evidence.
Parkinson's disease (PD) is associated with several non-motor symptoms, such as behavioral changes, urinary dysfunction, sleep disorders, fatigue and, above all, gastrointestinal (GI) dysfunction, including gastric dysmotility, constipation and anorectal dysfunction. Delayed gastric emptying, progressing to gastroparesis, is reported in up to 100% of patients with PD, and it occurs at all stages of the disease with severe consequences to the patient's quality of life. The presence of α-synuclein (α-syn) aggregates in myenteric neurons throughout the digestive tract, as well as morpho-functional alterations of the enteric nervous system (ENS), have been documented in PD. In particular, gastric dysmotility in PD has been associated with an impairment of the brain-gut axis, involving the efferent fibers of the vagal pathway projecting directly to the gastric myenteric plexus. The present review intends to provide an integrated overview of available knowledge on the possible role played by the ENS, considered as a semi-autonomous nervous network, in the pathophysiology of gastric dysmotility in PD. Particular attention has been paid review how translational evidence in humans and studies in pre-clinical models are allowing a better understanding of the functional, neurochemical and molecular alterations likely underlying gastric motor abnormalities occurring in PD.
Department of Clinical and Experimental Medicine, University of Pisa, Via Roma 55, 56126, Pisa, Italy.
Carolina
C
Pellegrini
Department of Clinical and Experimental Medicine, University of Pisa, Via Roma 55, 56126, Pisa, Italy.
Luca
L
Antonioli
Department of Clinical and Experimental Medicine, University of Pisa, Via Roma 55, 56126, Pisa, Italy. Electronic address: r.colucci@med.unipi.it.
Rocchina
R
Colucci
Department of Pharmacy, University of Parma, Parco Area delle Scienze 27/A, 43124, Parma, Italy.
Vigilio
V
Ballabeni
Department of Pharmacy, University of Parma, Parco Area delle Scienze 27/A, 43124, Parma, Italy.
Elisabetta
E
Barocelli
Department of Clinical and Experimental Medicine, University of Pisa, Via Roma 55, 56126, Pisa, Italy.
Nunzia
N
Bernardini
Department of Clinical and Experimental Medicine, University of Pisa, Via Roma 55, 56126, Pisa, Italy.
Corrado
C
Blandizzi
Department of Clinical and Experimental Medicine, University of Pisa, Via Roma 55, 56126, Pisa, Italy.
Matteo
M
Fornai
D000818:Animals; D002766:Cholecystokinin / Q000502:physiology; D004525:Efferent Pathways / Q000503:physiopathology; D017615:Enteric Nervous System / Q000737:chemistry / Q000473:pathology; D005746:Gastric Emptying; D005769:Gastrointestinal Motility; D018589:Gastroparesis / Q000209:etiology* / Q000503:physiopathology; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D008959:Models, Neurological; D009469:Neuromuscular Junction / Q000503:physiopathology; D016627:Oxidopamine / Q000633:toxicity; D010300:Parkinson Disease / Q000150:complications / Q000209:etiology / Q000503:physiopathology*; D020734:Parkinsonian Disorders / Q000503:physiopathology; D066329:Protein Aggregates; D051381:Rats; D012402:Rotenone / Q000633:toxicity; D057170:Translational Research, Biomedical; D014630:Vagus Nerve / Q000503:physiopathology; D051844:alpha-Synuclein / Q000032:analysis / Q000235:genetics
D066329:Protein Aggregates; D051844:alpha-Synuclein; D012402:Rotenone; D016627:Oxidopamine; D002766:Cholecystokinin
Gastric motility; Gastric neuromuscular functions; Parkinson's disease; Preclinical models of Parkinson's disease