Role of the vagus in the reduced pancreatic exocrine function in copper-deficient rats

Tanja Babic, Ruchi Bhagat, Shuxia Wan, Kirsteen Browning, Michael Snyder, Samuel R. Fortna, Renato Alberto Travagli

Research output: Contribution to journalArticle

4 Citations (Scopus)

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 copperdeficient 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 copperdeficient 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.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume304
Issue number4
DOIs
StatePublished - Feb 15 2013

Fingerprint

Copper
Neurons
Sincalide
Exocrine Pancreas
Immunohistochemistry
Efferent Neurons
Diet
Pancreatic Polypeptide
Neural Pathways
Nitric Oxide Synthase Type I
Choline O-Acetyltransferase
Tyrosine 3-Monooxygenase
Microinjections
Motor Neurons
Caseins
Ganglia
Brain Stem
Atrophy
Central Nervous System

All Science Journal Classification (ASJC) codes

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)

Cite this

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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 copperdeficient 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 copperdeficient 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.",
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Role of the vagus in the reduced pancreatic exocrine function in copper-deficient rats. / Babic, Tanja; Bhagat, Ruchi; Wan, Shuxia; Browning, Kirsteen; Snyder, Michael; Fortna, Samuel R.; Travagli, Renato Alberto.

In: American Journal of Physiology - Gastrointestinal and Liver Physiology, Vol. 304, No. 4, 15.02.2013.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Role of the vagus in the reduced pancreatic exocrine function in copper-deficient rats

AU - Babic, Tanja

AU - Bhagat, Ruchi

AU - Wan, Shuxia

AU - Browning, Kirsteen

AU - Snyder, Michael

AU - Fortna, Samuel R.

AU - Travagli, Renato Alberto

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AB - 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 copperdeficient 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 copperdeficient 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.

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