Quantitative analysis of calcium-binding proteins in the hypothalamus of humans diagnosed with major depressive disorder and schizophrenia

Krolewski DM, Medina A, Burke S, Bunney WE, Myers RM, Barchas JD, Schatzberg AF, Jones EG, Akil H, Watson SJ
Society for Neuroscience. 2011.


The “EF-hand” family calcium-binding proteins calretinin (CR), calbindin (CB), and parvalbumin (PV) has been used previously to delineate distinct neuronal subpopulations and glean insight into neuronal excitability in the central nervous system. Several human post-mortem studies suggest that alterations in the regulation of this gene family are associated with psychiatric illness, particularly in the neocortex and hippocampus. The hypothalamus, which has been linked to both major depressive disorder (MDD) and schizophrenia (SZ) by way of heightened hypothalamic-pituitary-adrenal (HPA) axis activity, displays a characteristic neuroanatomical pattern of CR, CB, and PV distribution. However, hypothalamic nucleus-specific regulation of these calcium-binding proteins in subjects diagnosed with such disorders has been relatively less investigated. Therefore, the aim of the present study is to examine potential differences in CB, CR, and PV mRNA expression within discrete hypothalamic nuclei of post-mortem human subjects diagnosed with MDD and SZ. To achieve this, frozen hypothalamic blocks from normal controls, MDDs, and SZs were sectioned at 10µm on a cryostat and in situ hybridization was performed utilizing radiolabeled cRNA probes for CB, CR, and PV. Then, employing a neuropeptide mRNA-based hypothalamic map generated by the Pritzker Neuropsychiatric Disorder Research Consortium (Krolewski et al., 2010) as a guide, individual subjects were aligned by homologous regions. An extensive quantitative analysis of CR, CB, and PV mRNA throughout the rostral-caudal extent of the human hypothalamus was subsequently undertaken. Based upon differential behavioral-related functionality, areas of particular interest included the paraventricular, dorsomedial, ventromedial, and posterior hypothalamic nuclei as well as the mammillary bodies. The results of this investigation describing calcium-binding protein gene regulation will serve to further elucidate prospective changes in the excitability of specific hypothalamic neuronal populations in MDD and SZ. The authors want to thank the members of Pritzker Neuropsychiatric Disorder Research Consortium.