Analysis of corticotropin-releasing hormone and tyrosine hydroxylase in the paraventricular and supraoptic hypothalamic nuclei of human depressed subjects
Krolweski DM, Medina A, Bunney WE, Myers RM, Barchas JD, Schatzberg AF, Akil H, Watson SJ
Society for Neuroscience. 2013.
Corticotropin-releasing hormone (CRH) and the catecholamine-synthesizing enzyme tyrosine hydroxylase (TH) are differentially expressed by neuronal subpopulations in the human paraventricular (PVN) and supraoptic (SON) hypothalamic nuclei. Previous studies suggest that PVN CRH gene expression changes contribute to an altered hypothalamic-pituitary adrenal (HPA) axis in humans diagnosed with major depressive disorder (MDD). The aim of the present study is to further investigate hypothalamic CRH mRNA regulation in MDD and determine its relationship to TH mRNA expression. To achieve this, frozen hypothalamic blocks from normal controls and MDDs were sectioned at 10µm on a cryostat and in situ hybridization (ISH) was subsequently performed utilizing radiolabeled cRNA probes for CRH and TH. Then, using a neuropeptide mRNA-based hypothalamic map generated by the Pritzker Neuropsychiatric Research Consortium (Krolewski et al., 2010) as a guide, individual subjects were then anatomically aligned. Our preliminary results show that neither expression of CRH (in the PVN) nor TH mRNA (PVN and SON) is different between controls and MDDs. In addition, PVN expression of CRH and TH mRNA signals were not correlated within individuals from control or MDD groups. However, TH mRNA in the PVN and SON were significantly correlated with each other in both control and MDD subjects. Currently, double-label ISH experiments are being conducted to determine the extent of TH co-localization with other HPA axis neuropeptides including CRH, arginine-vasopressin, and oxytocin. The results of this investigation describing both distribution of TH mRNA and its regulation will serve to further elucidate prospective changes in hypothalamic function in MDD. The authors want to thank the members of Pritzker Neuropsychiatric Disorder Research Consortium. Support: The Pritzker Neuropsychiatric Research Consortium and NIMH Conte Center Grant #L99MH60398.