Role of Sensory Circumventricular Organs in the Function of Hormones Affecting Feeding and Energy Balance
Date
2014-09-19
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Abstract
The subfornical organ (SFO) is a sensory circumventricular organ implicated in the regulation of fluid homeostasis and cardiovascular functions and characterized by the presence of receptors for a number of peripheral signals affecting food intake and energy balance such as leptin and cholecystokinin (CCK). CCK is an intestinal satiety hormone affecting short and long term energy balance. Given the importance of CCK in energy homeostasis and the presence of its receptors in the SFO, the objective of this thesis was to study the effect of CCK on the activity of the SFO using the area postrema (AP) and the nucleus of the solitary tract (NTS) as positive control regions. The effect of exogenous CCK-8 on the activity of the SFO neurons was examined using the functional activation markers c-Fos and p-ERK. CCK increased c-Fos immunoreactivity in the NTS and the AP as well as in the SFO compared to controls. Blockade of CCKR1 reduced the effects of CCK in the AP and the NTS, but not in the SFO, while antagonism of CCKR2 blocked CCK-induced SFO activation. Rats subjected to subdiaphragmatic vagotomy were used to study the contribution of the vagus nerve to CCK-induced effect on the SFO. It was found that CCK-induced activation of SFO was not dependent on an intact vagus, contrary to CCK-induced increase in c-Fos in the AP and the NTS which was abolished by vagotomy. Then, the effect of endogenous CCK was studied using meal-induced release of CCK which, similar to the effect of exogenous CCK, resulted in increased c-Fos activation. In a model of high fat diet (HFD) induced obesity, the effect of CCK on c-Fos expression in the AP and NTS was abolished. Surprisingly, HFD-fed rats experienced high basal c-Fos levels which made it impossible to investigate the effect of CCK in the SFO. In conclusion, these results show that SFO is a potential target for the actions of exogenous and endogenous CCK. These actions are not dependent on the vagus nerve. HFD induces changes in SFO activity evident by increased basal c-Fos immunoreactivity within the SFO of HFD-fed rats.
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Neuroscience, Physiology, Pharmacology
Citation
Ahmed, A. S. (2014). Role of Sensory Circumventricular Organs in the Function of Hormones Affecting Feeding and Energy Balance (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/27684