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A nigro‐vagal pathway controls colonic motility and may be impaired in a model of environmental Parkinson’s disease
Author(s) -
Nanni Giorgia,
Travagli R. Alberto
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.03531
Subject(s) - dorsal motor nucleus , medicine , endocrinology , vagus nerve , gastroparesis , area postrema , gastric emptying , stomach , central nervous system , stimulation
Parkinson’s disease (PD) is a neurodegenerative disorder characterized by motor deficits caused by the loss of substantia nigra pars compacta (SNpc) dopaminergic neurons. It is well known that the majority of PD patients experience gastrointestinal (GI) dysfunctions such as gastroparesis, impaired swallowing and severe constipation. Upper GI tract functions are modulated by vagal reflexes, the central neurocircuit of which are located in the dorsal vagal complex (DVC, i.e. dorsal motor nucleus of the vagus (DMV), nucleus tractus solitarius and area postrema). We discovered a monosynaptic nigro‐vagal pathway recently that modulates gastric tone and motility and is impaired in an environmental PD model induced by oral administration of subthreshold doses of paraquat (P) and lectin (L). It is not known, however, whether this pathway also modulates colonic motility and whether the P+L model of PD decreases intestinal transit. Proximal colonic motility and tone were recorded with a strain gauge aligned with the colonic circular smooth muscle, approximately 3 cm distal to the ileal‐cecal valve. Microinjections of the ionotropic glutamate selective agonist, NMDA, were made at the level of the SNpc (5nmoles/210nL) and the effects on colonic motility and tone assessed. Microinjection of NMDA, but not vehicle, increased colonic tone (472±54mg) and motility (+358±166% of baseline; N=2). Gastro‐cecal transit, an indicator of intestinal motility, was measured using the 13 C lactose ureide‐ breath test. Female rats had a slower gastro‐cecal transit time (178±24 min, N=4) than male rats (138±1.5 minutes, N=3). Treatment with P+L delayed gastro‐cecal transit time to 272±18 minutes (N=3). These data suggest that the nigro‐vagal pathway also modulates colonic motility and the P+L model of PD delayes intestinal transit and thus may be a useful model to study PD‐related constipation. Support or Funding Information supported by NIH grant DK‐55530 to R. Alberto Travagli