Human Fetal Cortex Research Articles

Cytomegalovirus replicates efficiently in human kidney mesangial cells.

Human cytomegalovirus (HCMV) is a major renal pathogen in congenitally infected infants and renal allograft recipients. We postulated that a specific renal cell type was involved in HCMV infection and reactivation. Human fetal kidney cortex cell cultures were assayed for their ability to support HCMV infection. Infectious center assays indicated that the low level of viral replication observed by virus yield assay occurred from a fraction of the cells in the mixed cultures. Virus-specific immunofluorescence and in situ hybridization documented the presence of HCMV-specific protein and nucleic acid, respectively, in a morphologically distinct cell type. These cells were purified, were identified as kidney mesangial cells, and were observed to support efficient HCMV replication. Our research identifies mesangial cells as a renal cell type that supports HCMV replication and provides evidence to implicate these cells in the pathogenesis of HCMV-induced renal disease.

Human brain synapses during early prenatal development

The principles governing development of the human brain, especially in the early period of its antenatal ontogeny, haverecently assumed particular importance. The undoubted key factor in individual formation of the human brain is early synaptogenesis, which leads to the appearance of the first neuronal nets, responsible for the formation of the specific functions of this developing organ. However, the process of formation of synaptic connections in the presumptive human brain and, in particular, in its cerebral cortex, has received very little study. We could find only one reference [i] in which true synaptic interneuronal junctions were described in the cerebral cortex of human fetuses, the earliest of which was aged 9 weeks.

ALS cerebrospinal fluid enhances human foetal astroglial cell proliferation in vitro.

Studies on the cerebrospinal fluid (CSF) of patients with amyotrophic lateral sclerosis (ALS) are relatively few and somewhat unclear. Recently, we were unable to demonstrate a cytotoxic effect of ALS sera on human central nervous system (CNS) cultures from 15 - 20 week old human foetuses, confirming the negative therapeutic effects obtained using plasma-exchange in affected patients[l]. We decided to study the effects of ALS-CSF on human foetal motor cortex in vitro. This tissue can grow in vitro in the presence of a standard tissue culture medium which contains 10% normal CSF and provides a sensitive assay for trophic factors and toxic substances of clinical relevance. ALS-CSF induces a significant glial cell proliferation in vitro. Indirect immunofluorescence techniques were used to identify the atroglial proliferating cells.

Indoleamine and catecholamine concentrations in the mid-term human fetal brain

Because of the likelihood that androgen-induced sex specific brain differentiation is mediated by various neurotransmitters, their concentrations were measured in the mid-term human fetal hypothalamus, cortex and cerebrospinal fluid (CSF). Tissue was collected from 32 hysterotomy specimens aged from 10 to 23 weeks, immediately frozen in liquid nitrogen, and stored at −20°C. 5-Hydroxytryptamine (5-HT), 5-hydroxy indole acetic acid (5-HIAA), norepinephrine (NE) and dopamine (DA) levels were measured by a fluorometric assay. Cord serum testosterone levels were measured by radioimmunoassay. In the male fetuses, hypothalamic concentrations of 5-HT, 5-HIAA and NE were all significantly increased in comparison to those in the cortex. Because the number of female fetuses was small, only the 5-HIAA levels were seen to be significantly higher in the hypothalamus than in the cortex. In the CSF from fetuses of both sexes, the DA levels were greatly raised. Concentrations of NE were significantly higher in male fetuses aged from 14–16 weeks, a time when plasma testosterone levels are also elevated. It is hypothesized that the raised plasma testosterone and hypothalamic NE concentrations are inter-related.

Development of the Human Fetal Auditory Cortex: Growth of Afferent Fibres

The sequential development and growth of the subcortico-cortical fibres have been studied by means of acetylcholinesterase (AChE; acetylcholine acetylhydrolase; EC 3.1.1.7) histochemistry on the serial sections obtained from brains of human fetuses ranging from 10 to 28 weeks of gestation. It was found that thalamic and basal telencephalic fibres approaching the fetal auditory cortex have very strong AChE reactivity during a prolonged period of growth. In the youngest fetuses (10.5 weeks) a prominent fibre system was seen emerging from the ventroposterior thalamic territory while the auditory neopallium was free of AChE staining. In older fetuses (16-18 weeks) AChE-positive fibres originating in the ventroposterior thalamus and basal telencephalon penetrate the 'subplate layer' of the auditory cortex. On the basis of AChE reactivity of the 'subplate layer' the auditory cortex can be delineated from the surrounding neocortical areas. In the oldest fetuses (22-28 weeks) AChE-positive fibres of thalamic origin penetrate the developing cortical plate of the auditory cortex.

Development of acetylcholinesterase (AChE) staining in human fetal auditory cortex.

In this study acetylcholinesterase (AChE) staining methods have been used to demonstrate the development of the prospective afferent fibres of auditory cortex in human fetuses ranging between 8 and 28 weeks of gestation. Earliest AChE positive staining was found in fetuses at 20--24 weeks in the neuropil of the marginal zone and throughout subplate layer of the auditory cortex. On the basis of this characteristic AChE staining pattern, the auditory cortex may be delineated from surrounding cortical areas. At 24--26 weeks, during intensive lamination of the cortical plate, AchE-positive reaction appears in the deep part of the cortical plate. In the oldest fetuses (28 weeks) a columnar pattern of vertical, darkly stained zones was seen in the middle third of the cortical plate. We conclude that AChE staining is characteristically distributed within cytoarchitectonic compartments and 'synaptic' layers of the developing auditory cortex. The AChE-positive layers coincide with the laminar pattern of synpatogeneis. Thus, AChE-positive reaction during development may serve as a parameter of cortical afferent (thalamic?) innervation of the auditory cortex. In addition, AChE reactivity may indicate the specific transmitter nature of the afferent fibres in the auditory cortex.

The Laminar Organization of the Prospective Auditory Cortex in the Human Fetus

The prospective auditory cortex was analysed in human fetuses at 11--13,5 post-ovulatory weeks with Nissl, Golgi and E.M. techniques. At 11--12 weeks, marginal, cortical plate, intermediate, subventricular and ventricular layers were recognized. Post-migratory neurons with developing dendrites were seen in marginal layer, cortical plate and superficial part of the intermediate zone only. At 12--13,5 weeks the superficial part of the intermediate zone is transformed into the true cortical layer--"subplate layer"--characterized by maturing neurons with growing dendrites, fine axonal arborization and low cell density. The neuronal circuitry elements are thus present very early in the prospective auditory cortex and distributed throughout the deep cortical plate of the "subplate layer" corresponding to the synaptic territory of other areas of the human fetal cortex.

The Ontogenesis of Human Fetal Hormones. IV. Somatostatin, Luteinizing Hormone Releasing Factor, and Thyrotropin Releasing Factor in Hypothalamus and Cerebral Cortex of Human Fetuses 10-22 Weeks of Age

Somatostatin, LRF, and TRF were measured by radioimmunoassay in extracts of hypothalami obtained from human fetuses between 10 to 22 weeks gestation. Iodinated LRF and somatostatin eluted mainly after the iodide peak (Kd ∼ 2), free of the unlabeled factor when purified on Sephadex G25 with 0.1M acetic acid as eluant. Of 3 anti- LRF sera used, one did not recognize any of 21 LRF fragments but could detect analogs with changes in position 2 and 8; a second only recognized the 7–10 C-terminal sequence, and the third was directed against positions 5–9. Hypothalamic or brain extracts produced parallel displacement in each radioimmunoassay. Somatostatin was present in 43/44 fragments: mean content in 44 hypothalami was 14.9 ± 2.0 ng, concentration 16.8 ± 2.2 pg/mg; in 25/27 cerebral cortex tissues, 4.2 ±1.1 pg/mg. There was weakly positive correlation between hypothalamic somatostatin and gestational age in the 10 to 22 week period (r = 0.388, P < 0.01). The mean content of LRF in 33/44 hypothalami was 1.53 ± 0...

Hypothalamic monoamines in human fetuses.

Dopamine, noradrenaline, and serotonin concentrations in human fetal hypothalamus, striatum, and neopallial cortex are rather low with the exception of a high hypothalamic dopamine level. The catecholamine fluorescence appears in the hypothalamus during the 10th fetal week, and in the median eminence during the 13th week. On the basis of these observations, it is suggested that the hypothalamic monoaminergic mechanism is present and probably functioning in the human fetal brain.

Human fetal cerebellar cortex: organization and maturation of cells in vitro.

Human fetal cerebellar cortex was maintained up to 5 months in vitro. Important features included early migration of granule neurons followed by maturation of Purkinje and granule neurons. Unique areas of organization developed in which a rim of leptomeningeal cells surrounded an explant and its outgrowth zone; these areas subsequently grew as well-defined units.

Metabolism of dehydroepiandrosterone by the separated zones of the human foetal and newborn adrenal cortex.

SUMMARY An ultramicrochemical technique has been applied to the study of the metabolism in vitro of [3H]DHA in the separated adult and foetal zones of the human adrenal gland. Evidence has been found for the formation of DHA sulphate and androstenedione in the adult and foetal zone, and whole adrenal gland preparations obtained from one newborn hydrocephalic infant and two mid-term foetuses, and also for the formation of 1 1β-hydroxyandrostenedione in the adult zone tissue from the hydrocephalic infant. In all experiments, more DHA was converted to DHA sulphate by the foetal zone (21–27% conversion) than by the adult zone (5–7% conversion), whereas more androstenedione was formed in the adult zone than in the foetal zone. At mid-term less than 0·6% of [3H]DHA was converted to androstenedione compared with 33 and 3·4% conversion by the adult and foetal zone tissue, respectively, from the hydrocephalic infant. These results are discussed in relation to perfusion studies of the human foetus and previous in vitro and histochemical investigations of the human foetal adrenal gland.

Hydroxysteroid dehydrogenases in the human adrenal cortex.

SUMMARY The histochemical utilization of 3α-, 3β-, 6β-, 11α-, 11β-, 12α-, 16α-, 16β-, 17α-, 17β-, 20α-, 21- and 24-hydroxysteroids by three normal adult human adrenal glands, two human foetal adrenal glands, three adrenals from patients with Cushing's syndrome and one adrenal adenoma are described. The normal adult human adrenal showed high 16β-hydroxysteroid dehydrogenase activity in the zona glomerulosa. Activity restricted to the outer part of the zona fasciculata was recorded with 3α-, 3β-, 6β-, 11β-, 16α-, 16β-, and 17β-hydroxysteroids. The zona reticularis utilized 3α-, 3β-, 11β-, 16β- and 17β-hydroxysteroids less well than the zona fasciculata. The adrenals of Cushing's syndrome showed activity only for 3β- and 16β-hydroxysteroid dehydrogenases; this activity was noted in all three zones. The activity pattern of the adrenal adenoma resembled that of the normal adult human adrenal except that greater activity for 16α-hydroxysteroid dehydrogenase was noted. The foetal part of the human foetal cortex was extremely active, showing 3α-, 3β-, 6β-, 11β-, 12α-, 16α-, 16β-, 17β-, 20β- and 21-hydroxysteroid dehydrogenase activity. The definitive cortex behaved similarly to the adult gland and possessed 3α-, 3β-, 11β-, 16β- and 17β-hydroxysteroid dehydrogenases; some evidence of zoning of the definitive cortex was seen with the 16β-hydroxysteroid. The relevance of these findings in the light of current knowledge of adrenal zonation is discussed.