A comparative anatomical assessment of gene expression patterns for calcium-binding proteins and gad67 in the human and rhesus monkey hypothalamus.
D. M. KROLEWSKI; A. MEDINA; I. A. KERMAN; R. BERNARD; S. BURKE; E. G. JONES; W. E. BUNNEY; H. AKIL; S. J. WATSON
Society for Neuroscience. 2008.
The localization of calcium-binding proteins (CBPs) calbindin (CB), calretinin (CR), and parvalbumin (PV) has classically been used to delineate distinct neuronal populations that, interestingly, often co-express gamma-aminobutyric acid (GABA) in many brain nuclei. The clinical relevance of these genes has been previously demonstrated by their dysregulation in the cortex and hippocampus of subjects with mood disorders. Therefore, preliminary to quantitative studies, we sought to examine the spatial relationship between the expression of CB, CR, PV, and that of the GABA synthesizing enzyme GAD67 in the human and rhesus monkey hypothalamus which has been less investigated. To accomplish this, frozen human and monkey brain were cut on a cryostat at 10Âµm with sections obtained about the extent of the hypothalamus originating from the region of the paraventricular nucleus (PVN) and ending at the mammillary bodies. Subsequently, adjacent sections were processed for in situ hybridization employing cRNA probes for CB, CR, PV, and GAD67 as well as arginine-vasopressin (AVP) to better demarcate the PVN and supraoptic nucleus (SON). With the aide of AdobeÂ® PhotoshopÂ® CS 8.0, digitized images were generated with probe signals color-coded and overlaid to visualize relative gene expression patterns. Amongst our findings, we show species similarities that include a relatively low abundance of signal for CBPs and GAD67 in the PVN and SON where AVP expression is concentrated. In addition, GAD67 expression is particularly strong in the periventricular region and a comparable differential medial-lateral gradient exists for CR and CB in the ventromedial nucleus. More caudally, there is considerable overlap between CB, CR, and GAD67 gene expression in the dorsal hypothalamus. Furthermore, PV is confined to the mammillary bodies in both species. These distribution patterns not only aide in the understanding of hypothalamic evolution, but also provide an anatomical map for future quantitative analysis of genes related to neuropsychiatric disorders.