title: Role of the vagus in the reduced pancreatic exocrine function in copper-deficient rats.
abstract: Copper plays an essential role in the function and development of the central nervous system and exocrine pancreas. Dietary copper limitation is known to result in noninflammatory atrophy of pancreatic acinar tissue. Our recent studies have suggested that vagal motoneurons regulate pancreatic exocrine secretion (PES) by activating selective subpopulations of neurons within vagovagal reflexive neurocircuits. We used a combination of in vivo, in vitro, and immunohistochemistry techniques in a rat model of copper deficiency to investigate the effects of a copper-deficient diet on the neural pathways controlling PES. Duodenal infusions of Ensure or casein, as well as microinjections of sulfated CCK-8, into the dorsal vagal complex resulted in an attenuated stimulation of PES in copper-deficient animals compared with controls. Immunohistochemistry of brain stem slices revealed that copper deficiency reduced the number of tyrosine hydroxylase-immunoreactive, but not neuronal nitric oxide synthase- or choline acetyltransferase-immunoreactive, neurons in the dorsal motor nucleus of the vagus (DMV). Moreover, a copper-deficient diet reduced the number of large (>11 neurons), but not small, intrapancreatic ganglia. Electrophysiological recordings showed that DMV neurons from copper-deficient rats are less responsive to CCK-8 or pancreatic polypeptide than are DMV neurons from control rats. Our results demonstrate that copper deficiency decreases efferent vagal outflow to the exocrine pancreas. These data indicate that the combined selective loss of acinar pancreatic tissue and the decreased excitability of efferent vagal neurons induce a deficit in the vagal modulation of PES.
authors.affiliation: Department of Neural and Behavioral Sciences, Penn State University College of Medicine, Hershey, PA 17033, USA.
authors.forename: Tanja
authors.initials: T
authors.lastname: Babic
authors.forename: Ruchi
authors.initials: R
authors.lastname: Bhagat
authors.forename: Shuxia
authors.initials: S
authors.lastname: Wan
authors.forename: Kirsteen N
authors.initials: KN
authors.lastname: Browning
authors.forename: Michael
authors.initials: M
authors.lastname: Snyder
authors.forename: Samuel R
authors.initials: SR
authors.lastname: Fortna
authors.forename: R Alberto
authors.initials: RA
authors.lastname: Travagli
mesh_terms: D000818:Animals; D002364:Caseins / Q000008:administration & dosage; D003300:Copper / Q000172:deficiency*; D019422:Dietary Sucrose / Q000494:pharmacology; D005260:Female; D005526:Food, Formulated; D008297:Male; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology; D010179:Pancreas / Q000294:innervation / Q000378:metabolism*; D010191:Pancreatic Polypeptide / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012844:Sincalide / Q000031:analogs & derivatives / Q000494:pharmacology; D014630:Vagus Nerve / Q000502:physiology*
chemical_list: C090019:8-sulfocholecystokinin octapeptide; D002364:Caseins; D019422:Dietary Sucrose; C082131:Ensure formulated food; D010191:Pancreatic Polypeptide; D003300:Copper; D012844:Sincalide