The central nervous system strongly influences gastric functions of acid secretion and motility, and plays a major role in many pathologic processes such as peptic ulcer disease, motility and eating disorders. Neuropeptides have an important role in how the brain modulates vagauy mediated functions, and may be involved in disease processes. Thyrotropin-releasing homione (TRH) and bombesin are two important neuropeptides influencing brain control of gastric function, with opposing actions on gastric secretion and motility when microinjected into the dorsal vagal complex (DVC). While physiologic responses to these two neuropeptides have been extensively studied, the anatomic basis of these responses remains poorly defined. The overall goal of this proposal is to better understand the origin, connectivity and terminal ultrastructure of TRH and bombesin containing neurons in the brain that influence the DVC in rats. First, the topographic organization of TRH-immunoreactive (IR) neurons and the location of bombesin-IR neurons projecting to the DVC wig be defined by combining retrograde neuronal tracing with immunohistochemistry. Second, the ultrastructure of bombesin terminals in the DVC will be studied using electron microscopy to determine the types of bombesin-IR synaptic structures present, their location, and their relationship to gastric motoneurons and TRH-IR nerve terminals. Third, neurons in central nervous system nuclei that innervate gastric vagal motoneurons will be mapped using pseudorabies virus, a new neuroanatomical tracer that crosses synapses. This tracer will be combined with immunohistochemistry to determine which TRH- and bombesin-IR neurons have direct connections with gastric vagal motoneurons. Fourth, the connectivity of divergent axon collaterals of TRH-IR raphe neurons will be defined by combining double retrograde tracing with immunohistochemistry.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08DK002094-03
Application #
3081028
Study Section
Diabetes, Endocrinology and Metabolic Diseases B Subcommittee (DDK)
Project Start
1991-09-30
Project End
1996-08-31
Budget Start
1993-09-01
Budget End
1994-08-31
Support Year
3
Fiscal Year
1993
Total Cost
Indirect Cost
Name
Thomas Jefferson University
Department
Type
Schools of Medicine
DUNS #
061197161
City
Philadelphia
State
PA
Country
United States
Zip Code
19107
Broussard, D L; Lynn, R B; Wiedner, E B et al. (1998) Solitarial premotor neuron projections to the rat esophagus and pharynx: implications for control of swallowing. Gastroenterology 114:1268-75
Lynn, R B; Bechtold, L S; Miselis, R R (1997) Ultrastructure of bombesin-like immunoreactive nerve terminals in the nucleus of the solitary tract and the dorsal motor nucleus. J Auton Nerv Syst 62:174-82
Lynn, R B; Cao, G Y; Considine, R V et al. (1996) Autoradiographic localization of leptin binding in the choroid plexus of ob/ob and db/db mice. Biochem Biophys Res Commun 219:884-9
Lynn, R B; Hyde, T M; Cooperman, R R et al. (1996) Distribution of bombesin-like immunoreactivity in the nucleus of the solitary tract and dorsal motor nucleus of the rat and human: colocalization with tyrosine hydroxylase. J Comp Neurol 369:552-70
Lynn, R B; Friedman, L S (1995) Irritable bowel syndrome. Managing the patient with abdominal pain and altered bowel habits. Med Clin North Am 79:373-90
Lynn, R B; Sankey, S L; Chakder, S et al. (1995) Colocalization of NADPH-diaphorase staining and VIP immunoreactivity in neurons in opossum internal anal sphincter. Dig Dis Sci 40:781-91
Lynn, R B; Friedman, L S (1993) Irritable bowel syndrome. N Engl J Med 329:1940-5