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P75NTR is Necessary for Activating AgRP Neurons to Regulate Feeding Behavior

Presenters Name: 
Dove-Anna Johnson
Primary Research Mentor: 
Christopher Deppmann
Secondary Research Mentor: 
Brandon Podyma
1:00 - 1:15
Time of Presentation: 
2019 - 1:00pm to 1:15pm
South Meeting Room
Presentation Type: 
Presentations Academic Category: 
Grant Program Recipient: 
Harrison Undergraduate Research Grant

Obesity leads to overactive hunger signals and difficulty limiting food intake. While some of the players in feeding behavior are known, such as leptin inhibition of feeding-promoting AgRP neurons, enhancing our understanding of feeding neurocircuits would provide new means of addressing obesity. Various receptors and proteins interact with these neurons, including the neurotrophic factor BDNF and its cognate receptor TrkB, where mutation of either leads to hyperphagia and obesity. The p75 neurotrophin receptor (p75NTR), another BDNF receptor involved in whole body metabolism, however, has gone unstudied in feeding behavior. To test p75NTR’s role in feeding, wildtype (WT) and p75NTR knockout (KO) mice were fasted overnight. Glucose, β-Ketone, and body weight measurements were taken before and after the fast, and showed normal peripheral control of metabolism. Strikingly, however, KO mice ate less when they were refed after the fast than WT controls. To rationalize the refeeding difference, we looked at hypothalamus activation. Immunofluorescence showed diminished arcuate cfos levels in KO mice after the fast compared to WT controls, suggesting that KO mice were not effectively activating these neurons. To localize this effect, we generated mice with deletion of p75NTR solely in AgRP neurons, and found that these mice recapitulated the feeding defect observed in the germline knockout. These results suggest that p75NTR is important in the activation of AgRP neurons following an overnight fast. Determining the role of p75NTR in regulating food intake will increase our knowledge about metabolic pathways and aid us in developing better treatment strategies for obesity.