29-30 January, 2020 - Szeged, Hungary


Abstract details

Expression of Tyrosine Receptor Kinase B in the dorsomedial hypothalamic nucleus of diabetic and control persons


Eva Renner1, Fanni Dóra12, Erzsébet Horváthné Oszwald2, Arpád Dobolyi23, Miklós Palkovits1

1 Human Brain Tissue Bank and Microdissection Laboratory, Semmelweis University, Budapest, Hungary; 2Laboratory of Neuromorphology, Department of Anatomy, Histology and Embryology, Semmelweis University, Budapest; 3MTA-ELTE Laboratory of Molecular and Systems Neurobiology, Department of Physiology and Neurobiology, Eötvös Loránd University and the Hungarian Academy of Sciences

Previous studies showed that brain-derived neurotrophic factor (BDNF) signalling through the Tyrosine Receptor Kinase B (TrkB) receptor plays a critical role in the control of energy balance in rats and that TrkB neurons in the dorsomedial hypothalamic nucleus (DMH) participate in the suppression of appetite. Now, we investigated the topographical distribution of TrkB-expressing neurons in the human DMH. In situ hybridization probes for TrkB were developed for radioactive in situ hybridization histochemistry. We found that a high number of neurons in the human DMH expressed TrkB and the presence of TrkB proteins was also demonstrated by using immunohistochemistry. We examined TrkB expression in post-mortem hypothalamus from five type 2 diabetic (T2DM) patients versus six control persons. Reduced TrkB expression was found in the DMH of T2DM subjects suggesting decreased BDNF signalling in T2DM. In rats, we reported previously that glucagon-like peptide-1 (GLP-1) and prolactin-releasing peptide (PrRP) of brainstem origin activate neurons in the DMH and contribute to satiation. Therefore, in the present study, we also addressed if GLP-1 and PrRP terminals influence TrkB neurons in the DMH. We found that GLP-1 and PrRP-fibres were abundant in the DMH. Their distributions overlapped with TrkB-expressing neurons within the nucleus and closely apposed them. Thus, the special role of TrkB in the hypothalamic food intake regulation reported previously in rats may also apply to human, and the activity of TrkB neurons in the DMH could be driven by ascending GLP-1 and PrRP fibres. Support: NKFIH 2017-1.2.1-NKP-2017-00002 (NAP2 program) for ER, FD and MP.