Immunocytochemical evidence of well‐developed dopaminergic and noradrenergic innervations in the frontal cerebral cortex of human fetuses at midgestation

Abstract

The catecholaminergic (CA) innervation of the frontal lobe was visualized in 20- to 24-week-old human fetuses with immunocytochemical techniques, by use of antibodies raised against three synthetic enzymes of the CA pathway, tyrosine-hydroxylase (TH), dopamine-beta-hydroxylase (DBH), and phenylethanolamine-N-methyltransferase (PNMT). DBH-like immunoreactivity (IR) was probably labeling the noradrenergic (NA) fibers and terminals in the cerebral cortex since no PNMT-IR fibers were detected. In double-labeling TH-DBH experiments, 92-95% of the DBH-IR afferents were not labeled with TH antibodies, indicating that TH-like immunoreactivity (TH-IR) was found primarily in dopaminergic (DA) fibers. Although cortical layering had not yet occurred at this stage, the widespread CA innervation observed in the different areas and layers of the fetal frontal cortex was comparable to that previously described in the adult (Gaspar, Berger, Febvret, Vigny, and Henry: J. Comp. Neurol. 279:249-271, '89). At midgestation, the distribution of CA innervation was region and laminar specific: 1) The densest dopaminergic innervation in the cerebral cortex was located caudal to the genu of the corpus callosum: TH-IR fibers were abundant throughout all layers, from the medial telencephalon (future cingulate) to the dorsal areas (presumed motor cortices) and the lateral insular areas; 2) TH-IR fibers were less dense in the rostral prefrontal cortical anlage; 3) DBH-IR noradrenergic afferents were less numerous than the dopaminergic ones in all the cortical areas studied; 4) in all areas, the highest amount of TH and DBH-IR terminals was found in the upper subplate and in the lower part of the cortical plate, followed by the molecular layer and the intermediate zone. The deep subplate exhibited a lower number of positive fibers but contained TH-IR cell bodies. The presence of dense CA innervation in the immature cortical anlage of the human frontal lobe does not exclude a reorganization of DA and NA innervations within the different cortical layers and areas during the protracted pre- and postnatal period of development.

Early microglial colonization of the human forebrain and possible involvement in periventricular white‐matter injury of preterm infants

“…The transient subplate appears early in the human fetal brain and disappears during the last third of gestation and early infancy (Kostovic & Molliver, 1974;Kostovic & Rakic, 1990). It contains mature neurons and receives the first afferent connections entering the cortex, most notably thalamocortical afferents (Shatz et al 1988;Allendoerfer & Shatz, 1994) and catecholaminergic axons (Verney et al 1993;Zecevic & Verney, 1995). These cortical afferents were restricted to the subplate-intermediate zone and did not penetrate the cortical plate, as shown for the catecholaminergic axons exhibiting tyrosine hydroxylase immunoreactivity (Fig.…”

Sculpting Cerebral Cortex with Serotonin in Rodent and Primate

“…In Rhesus monkey, the genesis of raphe neurons was detected in the first quarter of gestation (E28-E45, birth: E165) [139] and 5HT+ fibres were reported in the entorhinal cortex at E70, similarly to tyrosine-hydroxylase+ catecholaminergic axons [140]. In human cortical anlage, one can suggest that the early afferents of serotoninergic axons as described for the catecholaminergic afferents may penetrate the cortical anlage around GW8 and invade the fetal cortex at midgestation in a mature-like pattern [102,141]. In parallel, SERT expression in developing TCAs have been detected at GW10 in human cortical anlage [142].…”

Early neuromeric distribution of tyrosine-hydroxylase-immunoreactive neurons in human embryos

“…In the present investigation, we set out to determine these origins by studying the relevant segmental and dorsoventral relationships of tyrosine-hydroxylase-(TH)-expressing neurons in early human embryos at stages of development in which neuromeres can be identified morphologically. Although the development of human catecholamine cell groups has been studied several times Nobin and Björklund., 1973;Choi et al, 1975;Pickel et al, 1980;Pearson et al, 1980Pearson et al, , 1983Freeman et al, 1991;Verney et al, 1991Verney et al, , 1993Zecevic and Verney, 1995), practical difficulties usually have impeded observation of the most immature stages. The study by Verney et al (1991) on 5-week-old embryos and, more recently, the partial description of 3.5-and 4.5-week-old embryos by Almqvist et al (1996) Human embryos are difficult to obtain and process into high-quality histological preparations but have the advantages of a larger brain and a longer period of development, both of which emphasize developmental details that may pass unnoticed in the brains of rodents (see Levitt and Rakic, 1982).…”