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The organization of the human hypothalamus was studied in 31 brains aged from 9 weeks of gestation (w.g.) to newborn, using immunohistochemistry for parvalbumin, calbindin, calretinin, neuropeptideY, neurophysin, growth associated protein GAP43, synaptophysin and glycoconjugate, 3-fucosyl-N-acetyl-lactosamine. Morphogenetic periods 9-10 and 11-14 w.g. are characterized by differentiating structures of the lateral hypothalamic zone, which give rise to the lateral hypothalamus (LH) and posterior hypothalamus. The perifornical nucleus differentiates at 18 w.g., from LH neurons which remain anchored in the perifornical position while most of the LH cells are displaced laterally. A transient supramamillary nucleus was apparent at 14 w.g. but not after 16 w.g. As the ventromedial nucleus differentiated at 13-16 w.g., three principal parts; the ventrolateral, the dorsomedial and the shell were revealed by distribution of calbindin, calretinin and GAP43 immunoreactivity. Morphogenetic periods 15-17, 18-23 and 24-33 w.g. are characterized by differentiation of the hypothalamic core, in which calbindin positive neurons revealed the medial preoptic nucleus at 16 w.g. abutted laterally by the intermediate nucleus. The dorsomedial nucleus was clearly defined at 10 w.g. and consisted of compact and diffuse parts, an organization that was lost after 15 w.g. Differentiation of the medial mamillary body into lateral and medial was seen at 13-16 w.g. Morphogenetic period after 34 w.g. was marked by differentiation of midline zone structures including suprachiasmatic, arcuate and paraventricular nuclei. The findings of the present study provide for a better understanding of the structural organization of the adult human hypothalamus, produce new evidence for homologies with the better studied rat hypothalamus and underpin staging system for fetal human hypothalamic development.

A variety of histochemical findings have contributed to a more differentiated architectonical description of the bed nucleus of the stria terminalis (BNST) in the mammalian brain. However, in the human brain investigations of the chemoarchitecture of this nucleus have been rare. Therefore we chose this region in six human autopsy brains in order to map the distribution patterns of 13 immunohistochemical markers for neurotensin (NT), neuropeptide Y (NPY), somatostatin (SOM), enkephalins (ENK), vasoactive intestinal polypeptide (VIP), substance P (SP), neurophysins (NPH), glial fibrillary acid protein, 3-fucosyl-N-acetyl-lactosamine epitope, myelin basic protein (MBP), calbindin (CAB), synaptophysin (SYN) and chromogranin-A (CHR-A). Three chemoarchitectonically distinct areas could be defined. The lateral subdivision of the BNST contained high amounts of NPY and SP-fibre immunoreactivity and was further characterized by the occurrence of neurons labelled for NPY. The central subdivision of the BNST appeared as a histochemically clearly circumscribed compartment with massive fibre immunoreactivity for SOM, ENK, VIP, SYN, CHR-A, CAB as well as SOM, ENK, NT and CAB positive cells but lacked cytosolic or fibre-like immunolabel for NPY and SP. This structure was also ensheathed by myelinated fibres identified by means of MBP immunohistochemistry. The medial subdivision of the BNST showed moderate to high SP and NPY fibre immunoreactivity but lacked immunolabelled neurons and was only scarcely supplied with varicose or punctiform ENK immunoproduct. In the most posterior levels of our sections a cell group labelled for NPH was located lateral to the fornix columns. The lateral subdivision of the BNST (with NPY, SYN) and mainly the central BNST (with SOM, ENK, VIP, SYN and CHR-A) contributed to ventrolateral extensions of dense patchy fibre immunoreactivity throughout the basal forebrain region.

The distribution of the carbohydrate epitope 3-fucosyl-N-acetyl-lactosamine was investigated on paraffin sections of the normal adult human central nervous system by means of immunohistochemistry, using the mouse monoclonal antibody anti-Leu-M1. This antibody is one among many others recognizing this epitope, which is also known as stage specific embryonic antigen I or X-hapten. We found this epitope predominantly localized on astrocytes especially along their numerous cell processes. There was a striking association of immunoreactive astrocytes with intracortical blood vessels and with distinct brain areas. Leu-M1-positive oligodendrocytes were present in the white matter with highest densities in the centrum semiovale and lateral pontine regions. Most cells of the ependymal lining, including tanycytes, showed Leu-M1 immunoreactivity but there was some topographical variability. Double-labelling experiments revealed that Leu-M1-positive glial cells may or may not be immunoreactive to glial fibrillary acidic protein or S-100 protein. The Leu-M1 antibody also stained a large number of different sets of neurons from cerebral cortex to spinal cord. Groups of immunostained cells were found in the hypothalamus, dorsal thalamus, ventral and mesial mesencephalic tegmentum, and several lower brainstem regions such as the lateral reticular formation, the raphe nuclei and the pons. Leu-M1 immunoreactivity appeared associated to neurochemically specified neuronal cell groups such as the mesencephalic dopaminergic system and the hypothalamic neurophysin system. In summary, our study demonstrates a distinct topographical distribution of the Leu-M1 epitope in the adult human central nervous system. Its exact functions, however, have not yet been elucidated, but there is evidence for the involvement of this epitope in cell-cell-adhesion and -interaction processes.