Prenatal alcohol exposure is a leading cause of interneuronopathy in humans

Alcohol affects multiple neurotransmitter systems, notably the GABAergic system and has been recognised for a long time as particularly damaging during critical stages of brain development. Nevertheless, data from the literature are most often derived from animal or in vitro models. In order to study the production, migration and cortical density disturbances of GABAergic interneurons upon prenatal alcohol exposure, we performed immunohistochemical studies by means of the proliferation marker Ki67, GABA and calretinin antibodies in the frontal cortical plate of 17 foetal and infant brains antenatally exposed to alcohol, aged 15 weeks’ gestation to 22 postnatal months and in the ganglionic eminences and the subventricular zone of the dorsal telencephalon until their regression, i.e., 34 weeks’ gestation. Results were compared with those obtained in 17 control brains aged 14 weeks of gestation to 35 postnatal months. We also focused on interneuron vascular migration along the cortical microvessels by confocal microscopy with double immunolabellings using Glut1, GABA and calretinin. Semi-quantitative and quantitative analyses of GABAergic and calretininergic interneuron density allowed us to identify an insufficient and delayed production of GABAergic interneurons in the ganglionic eminences during the two first trimesters of the pregnancy and a delayed incorporation into the laminar structures of the frontal cortex. Moreover, a mispositioning of GABAergic and calretininergic interneurons persisted throughout the foetal life, these cells being located in the deep layers instead of the superficial layers II and III. Moreover, vascular migration of calretininergic interneurons within the cortical plate was impaired, as reflected by low numbers of interneurons observed close to the cortical perforating vessel walls that may in part explain their abnormal intracortical distribution. Our results are globally concordant with those previously obtained in mouse models, in which alcohol has been shown to induce an interneuronopathy by affecting interneuron density and positioning within the cortical plate, and which could account for the neurological disabilities observed in children with foetal alcohol disorder spectrum.

Early development of human ganglionic eminences assessed in vitro by using 7.04 Tesla micro-MRI – a pilot study

Background and aims. Ganglionic eminences are temporary structures which appear during the 5th week post-fertilization on the floor of telencephalic vesicles and disappear until the 35th week of gestation. The aim of this descriptive study of morphological research is to depict the ganglionic eminences within the embryonic and early fetal brains by using micro-MRI. Methods. Six human embryos and fetuses ranging from 21 mm crown-rump length CRL (9 gestational week GW) to 85 mm CRL (14 GW) were examined in vitro by micro-MRI. The investigation was performed with a Bruker BioSpec 70/16USR scanner (Bruker BioSpin MRI GmbH, Ettlingen, Germany) operating at 7.04 Tesla. Results. We describe the morphological characteristics of the ganglionic eminences at different gestational ages. The acquisition parameters were modified for each subject in order to obtain an increased spatial resolution. The remarkable spatial resolution of 27 µm/voxel allows visualization of millimetric structures of the developing brain on high quality micro-MR images. Conclusion. In our study we give the description of the ganglionic eminences within the embryonic and early fetal brains by using micro-MRI, which have not been previously documented in literature. Micro-MRI provides accurate images, which are comparable with the histological slices.

Agenesis of the putamen and globus pallidus caused by recessive mutations in the homeobox gene GSX2

Congenital malformations of the basal ganglia are rare. De Mori et al. describe a novel syndrome of severe dystonic tetraparesis and intellectual impairment, with hypo/agenesis of the basal ganglia. The syndrome is caused by recessive mutations in GSX2, a homeobox gene expressed in ganglionic eminences and essential for basal ganglia development.

Coevolution in the timing of GABAergic and pyramidal neuron maturation in primates

The cortex of primates is relatively expanded compared with many other mammals, yet little is known about what developmental processes account for the expansion of cortical subtype numbers in primates, including humans. We asked whether GABAergic and pyramidal neuron production occurs for longer than expected in primates than in mice in a sample of 86 developing primate and rodent brains. We use high-resolution structural, diffusion MR scans and histological material to compare the timing of the ganglionic eminences (GE) and cortical proliferative pool (CPP) maturation between humans, macaques, rats, and mice. We also compare the timing of post-neurogenetic maturation of GABAergic and pyramidal neurons in primates (i.e. humans, macaques) relative to rats and mice to identify whether delays in neurogenesis are concomitant with delayed post-neurogenetic maturation. We found that the growth of the GE and CPP are both selectively delayed compared with other events in primates. By contrast, the timing of post-neurogenetic GABAergic and pyramidal events (e.g. synaptogenesis) are predictable from the timing of other events in primates and in studied rodents. The extended duration of GABAergic and pyramidal neuron production is associated with the amplification of GABAerigc and pyramidal neuron numbers in the human and non-human primate cortex.