The Functional Organization of the Developing Human Brain in Relation to Motor Deficits, Cognitive Impairment and Psychotic States

Abstract

The human developing brain displays transient architectonic features, i.e. prominent structures which are involved in fetal neuronal circuitries. The latter play a pivotal role in the establishment of mature projections. In the first part of this review, data are summarized that the ganglionic eminence (a conspicuous part of the telencephalic proliferative zone) serves as an intermediate target for growing axons. Bleedings occurring in the ganglionic eminence could therefore lead to subtle alterations in mature connectivities, which may account for cognitive deficits. Subtle alterations of neuronal morphology in fetal hydrocephalus are demonstrated and discussed to account for mental impairment. In the second part, data are presented which demonstrate the complex modes of neuronal migration, such as tangential and ventricle-directed migration. It is hypothesized that a disturbance of a certain mechanism of migration may be involved in the developmental origin of schizophrenia. In the third part, the putative role of a transient projection of the red nucleus in periventricular leukomalacia is shown. It is speculated that a continuous reduction of this (rubrospinal) projection is related to the delayed and gradual occurrence of spastic diplegia in infants with periventricular leukomalacia. On the whole, this review emphasizes that certain clinical observations and symptoms may be associated with transitory neuronal circuitries in the developing brain. Moreover, it is pointed out that the application of current concepts in neuronal migration may contribute to a better understanding of neuropathological alterations in schizophrenia.

Expression of the G-Protein-Coupled Receptor Endothelial Differentiation Gene-2 in the Developing Human Forebrain with Reference to Myelination

“…In prematurely born infants, intracranial hemorrhage constitutes a frequent CNS complication and is often correlated with impaired cognitive function and behavioral deficits during childhood. The ganglionic eminence is the predilection site of such bleedings in preterm infants [18][19][20]. In light of our findings, which provide further evidence for the ganglionic eminence being the origin of oligodendrocytes and underline its functional complexity, bleedings in this transient structure might have severe effects with regard to myelination and related ontogenetic processes.…”

Dichlorodiphenyltrichloroethane Specifically Depletes Dopaminergic Neurons in Primary Cell Culture

“…DDT is found to be one of those neurotoxins that are potentially harmful to neurons during growth and development [15,25,26]. Exposure of fetal and neonatal neurons to DDT and other neurotoxins may act through maternal routes, i.e., either by placental or milk feeding [1,16,17]. Our present findings thus imply that an early exposure to DDT may relate to the onset of Parkinson's disease in later stages of life.…”

“…Evidence has already indicated that an early exposure to toxins during embryonic development can be one of the factors that results in neuronal degeneration in later adult stages [16,17]. Motor deficits are among those neurological diseases that are caused by early exposures to neurotoxins [16].…”

“…Motor deficits are among those neurological diseases that are caused by early exposures to neurotoxins [16]. DDT is found to be one of those neurotoxins that are potentially harmful to neurons during growth and development [15,25,26].…”

“…This is important as exposure to DDT and other related toxins often occurs through breast milk feeding [1]. Moreover, early insults on neurons during embryonic and perinatal development are known to cause neuronal damages in later stages of life [16,17].…”