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Title: Melanocortin and serotonin interactions in the central regulation of energy balance
Author: Georgescu, Teodora
ISNI:       0000 0004 7229 1038
Awarding Body: University of Aberdeen
Current Institution: University of Aberdeen
Date of Award: 2017
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Obesity and its comorbidities are a global problem, leading to escalating healthcare costs and profound human suffering. With levels of obesity rising, the development of new therapies is imperative. Research into processes regulating energy homeostasis facilitates the development of novel interventions. This thesis explores neurocircuits that affect energy balance, focussing on the serotonin (5-hydroxytryptamine; 5-HT) and melanocortin systems – established modulators of feeding behaviour. I first examined factors influencing the activity of proopiomelanocortin (POMC) neurones, principal cellular effectors of the melanocortin system that reside in the arcuate nucleus of the hypothalamus (ARC) and the brainstem nucleus of the solitary tract (NTS), brain regions known to influence energy balance. Using immunohistochemical and electrophysiological techniques, I demonstrated that leptin and 5-HT-ergic compounds increase the activity of POMCNTS cells, revealing a potential mechanism for their anorectic effects. I then confirmed that lorcaserin, an agonist for the serotonin 2C receptor (5-HT2CR), increases the activity of POMCARC neurones, a response similar to that seen for other 5-HTergic compounds. Having re-affirmed the involvement of the 5-HT system in the modulation of energy balance, I lastly sought to understand how 5-HT neurones of the dorsal raphe nucleus (DRN), the largest 5-HT producing structure in the brain, are modulated by nutritional cues and metabolic state. I examined whether the activity of these cells can be directly modulated by nutrients and characterised the mechanism underpinning the responses observed. I showed that 5-HTDRN neurones are metabolically sensitive and possess ATP-sensitive potassium channels (KATP), suggesting an ability to match energy state to electrical activity. Finally, I show that individual nutrients directly affect the firing pattern of 5-HTDRN cells, with amino acids having the most pronounced effect. In conclusion, this thesis adds to our understanding of how the brain integrates peripheral signals within central circuits to produce the co-ordinated control of feeding behaviours.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: MSH (Hormone) ; Serotonin ; Bioenergetics