Cerebral regulation of energy expenditure by TRH+ neurons and CO2 chmosensation

Project Description:

Diseases like obesity, diabetes and hypertension are associated with the development of an endothelial dysfunction, leading to an impaired response to CO2 in brain vessels and the existence of chemosensory neurons. Neuronal subpopulations which mediate metabolic effects of CO2 comprise chemosensitive orexin neurons in the lateral hypothalamus and TRH neurons in the PVN. In this project we will focus on the role of hypothalamic neurons which are activated or inhibited by CO2 and investigate the consequences of CO2 dysregulation as induced by endothelial dysfunction in the brain on peripheral organ functions, especially the thermogenesis of BAT.


Experimental Methods:

• Working with genetically modified mice (knock-out mice), including breeding strategies
• Generation, production and icv application of rAAV vectors
• Phenotyping of mice including measurement of thermogenesis, energy expenditure and body weight
• Immunohistochemical analyses of TRH neurons and their projections
• DNA and RNA extraction
• PCR, qPCR

Publications

Müller-Fielitz, H., Stahr, M., Bernau, M., Richter, M., Abele, S., Krajka, V., Benzin, A., Wenzel, J., Kalies, K., Mittag, J., Heuer, H., Offermanns, S., and Schwaninger, M.: Tanycytes control the hormonal output of the hypothalamic-pituitary-thyroid axis. Nat Commun., vol. 8(1), , 2017, doi: 10.1038/s41467-017-00604-6