Elucidating thyroid hormone-mediated alterations in sympathetic nervous system signaling

Kornelia Johann, Center of Brain, Behavior and Metabolism, Lubeck, Germany

 

Aims

Hyperthyroidism has a high prevalence and treatment is well established, however the mechanisms underlying thyroid hormone-mediated hyperthermia still remain enigmatic.  In previous mouse studies we found evidence for alterations in sympathetic nervous system activity that could influence thermogenesis. 

With this grant, I would like to visit the laboratories of our collaborators, Dr Jeff Dalley at the Department of Psychology, University of Cambridge, UK and Dr Amy Warner, head of the Disease Model Core, at the University of Cambridge, UK to measure Norepinephrine content in various organs. 

As Dr Dalley and his colleagues are leading experts in this specific method, their knowledge will be of great value for my PhD project.  After learning the well-established protocol, I will analyse tissue samples from previous studies in hyperthyroid mice for their Norepinephrine content.  Specifically, I am interested in adrenergic activation of white and brown adipose tissue, as well as heart and liver. 

In order to quantify and normalise the data obtained in Dr Dalley's lab, I will measure protein content of the respective samples in the laboratory of our collaborator Dr Amy Warner. 

 

Evaluation

The aim of this project was to investigate Norepinephrine (NE) turnover in different tissues of hyperthyroid mice.  While the in vivo part was conducted in my laboratory in Lübeck, Germany, the ex vivo extraction and quantification of NE, Dopamine (DA) and Serotonin (5-HT) in different tissues was performed in Cambridge, UK. 

As the laboratory of Professor Jeff Dalley at the Department of Psychology was too crowded to accommodate me for the extraction part, I performed this, as well as the protein measurements in the laboratory of Professor Dr Antonio Vidal-Puig and Dr Amy Warner with the help of Dr Sam Virtue in the first 1.5 weeks in Cambridge.  Afterwards, I went to the laboratory of Professor Jeff Dalley in order to perform the HPLC measurements.  During the first three days in Professor Jeff Dalley's laboratory, I was testing various mobile phases in order to reliably detect NE, DA and 5-HT in all of my samples.  Although it took longer than expected to find suitable separation conditions, in the end I managed to measure all three neurotransmitters in all of my samples and obtained very interesting results:

As expected from previous data, the basal level of norepinephrine in brown and inguinal white adipose tissue seems to be reduced in hyperthyroidism.  Furthermore, also the turnover rate of NE in these tissues seems to be reduced.  This is very interesting, as previous studies from other labs indicated central activation of brown adipose tissue (BAT)which would need increased norepinephrine levels and NE turnover.  However, as we found a decrease in BAT activity on various levels in our study, we conclude now, that decreased sympathetic input is causing the observed decrease in BAT thermogenesis. 

 

Grant awarded: €2,218