|dc.description.abstract||The vagus nerve is the tenth cranial nerve, and it is involved in function of the respiratory, cardiovascular, and gastrointestinal systems. Vagal afferent neurons are capable of sensing many factors about the environment through a number of different receptors. These receptors include cholecystokinin (CCK) receptors, which are involved in satiety, endocannabinoid receptors, which are involved in satiety and inflammation, and TLR-4 receptors that bind to lipopolysaccharide (LPS) and induce inflammatory processes. All three of these receptors are located on vagal afferent neurons. The purpose of this project is to discover more about their effects on neuronal activation and the signal transduction pathways that are involved.
This dissertation details 1) the effect of an endocannabinoid agonist, CP 55,940, on neuronal activation by CCK in cultured vagal afferent neurons using immunohistochemistry, 2) the effect of CP 55,940 on neuronal activation by LPS in cultured vagal afferent neurons using immunohistochemistry, and 3) the effect of CP 55,940 on neuronal activation by LPS on pNF-κB, NF-κB, and SOCS-3 expression in whole nodose ganglia when treated in vitro using Western blotting.
The results of these studies have shown that pre-treatment with a CB1 receptor agonist, CP 55,940, causes a decrease in activation by CCK in vagal afferent neurons in culture. In addition, it has been shown that pre-treatment with CP 55,940 causes a decrease in vagal afferent neuron activation by LPS in culture. Lastly, the data have shown that LPS causes a decrease in cytoplasmic pNF-κB and NF-κB and an increase in SOCS-3 expression in nodose ganglia in vitro and that CP 55,940 causes a decrease in SOCS-3 expression after stimulation with LPS but does not cause a change in pNF-κB or NF-κB expression. Collectively, these studies have shown the effects of endocannabinoids on vagal afferent neuronal activation after treatment with two different stimuli and has aided in elucidating the signal transduction pathways involved.||