Abstract

Anatomical analysis of gene expression patterns in the paraventricular region of human hypothalamus

D. M. KROLEWSKI; A. MEDINA; I. A. KERMAN; R. BERNARD; S. BURKE; E. G. JONES; W. E. BUNNEY; R. M. MYERS; J. D. BARCHAS; A. SCHATZBERG; H. AKIL; S. J. WATSON
Society for Neuroscience. 2007.

Though the neurochemical organization of the hypothalamus is well characterized in rodents, less is known regarding humans. Therefore, we sought to determine the relationship between several locally expressed genes and estimate their relative localization to previously defined anatomical nuclei in human brain. To achieve this, we cryosectioned human hypothalamus and performed in situ hybridization to examine the mRNA expression of corticotrophin-releasing factor (CRF), arginine-vasopressin (AVP), orexin (ORX), melanin-concentrating hormone (MCH), and histidine decarboxylase (HDC). Digitized images developed from these experiments were then aligned with adjacent sections processed with modified Kluver¿s stain. Subsequently, a published human brain atlas was used to determine the approximate location of the various hypothalamic nuclei within the paraventricular region (PVR) of our tissue. A 3-dimensional reconstruction as well as an internal atlas was generated to visualize this relationship every 500µm about the extent of the PVR. Results showed that CRF and AVP were both strongly expressed within the paraventricular nucleus (PVN) whereas the latter was also prominently localized to the dorsolateral and ventromedial supraoptic nucleus. Moreover, this pattern remained consistent starting at the most rostral sections (PVN positioned below the fornix) and continued for approximately 3.5mm into the caudal PVR (PVN positioned above the fornix). ORX mRNA was notable throughout the most of the PVR with expression shifting rostrally from a scattered-like appearance in the ventral medial hypothalamus nucleus to a more remarkable appearance in the dorsal and dorsomedial nuclei of the caudal PVR. Similarly, MCH expression was dispersed rostrally, particularly within the lateral hypothalamic nucleus, and transitioned to a more intense signal in the areas of the dorsal, dorsomedial, and dorsolateral hypothalamic nuclei. HDC mRNA was largely confined to the lateral tuberal and tuberomam illary nuclei. These anatomical correlations offer additional insight into the organization of gene expression in the human hypothalamus. Furthermore, such distribution patterns will aide in providing an anatomical reference for future quantitative studies involving genes functionally related to neuropsychiatric disorders.