Developmental organization of neurophysin neurons in the human brain

Abstract

Neurophysin (NPH) was detected immunohistochemically in 34 human brains ranging in age from 10 weeks of gestation (wg) to 3 months postnatal. Weakly-stained NPH-immunoreactive (NPH-IR) cells were already aggregated in the lateral hypothalamus in the supraoptic nucleus at 10 wg, the first time point examined. From this time, there was a clear and consistent chronology in the first appearance of NPH-immunoreactivity in different cell groups progressing from the supraoptic nucleus at 10 wg to cells in the accessory NPH cell group at 13 wg, paraventricular nucleus at 14 wg, suprachiasmatic nucleus at 18 wg and various other well defined clusters in the basal forebrain at 18-20 wg. NPH-IR fibers were present in the hypothalamo-hypophyseal tract from 10 wg, and together with other available evidence, our findings suggest the presence of a potentially functional hypothalamohypophyseal system by the end of the first trimester. NPH staining patterns and orientations of cells suggest that NPH-IR cells originate from the region of the hypothalamic sulcus in a manner consistent with animal studies, and migrate to their settling areas before expressing NPH-immunoreactivity. In spite of the likelihood that most NPH-IR cells (with the probable exception of those in the suprachiasmatic nucleus) derive from a single primordium, the final organization of NPH-IR cells consists of many scattered groups, as seen in the late fetal period and mature brain. Developmental analysis provides further evidence that there is a high degree of conservation in the topographic organization of the numerous diverse NPH-IR cell groups in humans and other mammals, suggesting that the separation and organization of these groups may be of functional importance.

Interaction of perinatal and pre-pubertal factors with genetic predisposition in the development of neural pathways involved in the regulation of energy homeostasis

“…One of the problems in using rodent models as surrogates for human conditions in this research area is that there are critical differences in the timing of central nervous system development between humans and the rodents. For example, whereas the human hypothalamus is completely developed at birth (Ackland et al, 1983; Bugnon et al, 1982; Burford and Robinson, 1982; Koutcherov et al, 2002; Mai et al, 1997), most hypothalamic neurons differentiate into mature neurons at embryonic day 12–16 (E12–16) (Markakis, 2002), where birth of the pup occurs at ~E22. Furthermore, hypothalamic projections from the ARC to the PVN are not completed until P12–14 in rodents (Bouret et al, 2004a; Grove et al, 2003; Grove and Smith, 2003).…”

Developmental gene×environment interactions affecting systems regulating energy homeostasis and obesity

“…In non-human primates, hypothalamic neurogenesis occurs during the first few months of gestation [127]. Limited human studies suggest that early hypothalamic neurogenesis occurs during weeks 9–10 of gestation [128; 129; 130; 131; 132]. In non-human primates the anabolic NPY/AgRP ARC to PVN projections develop during the late second trimester (by gestational day 100).…”

Expression pattern of histaminergic neurons in the human fetal hypothalamus at second and third trimester

“…Hypothalamic development is considered to be initiated with cell proliferation in ventricular marginal zone adjacent to the wall of the third ventricle, followed by formation of neuroblasts or postmitotic cell populations external to the germinal layer during the second half of gestation in rat, 23,23,24 in the middle of gestation in cat, 25 and in the first quarter of gestation in the rhesus monkey. 22,26 Few reports on human fetal chemoarchitecture 27,28,29,30 and cytoarchitecture 31,32 suggest early hypothalamic neurogenesis. During development aggregates of compact cell groups termed nuclei or more dispersed populations termed areas, but the mechanism of such aggregation is still largely unclear.…”