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| Catherine L. Verney |
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INSERM E9935, Hôpital Robert Debré, Paris France
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Presentation: |
| 2002-10-08, 09:45-10:30 |
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| The neurotransmitters in the development of the human brain. |
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Neurotransmitters are defined as substances synthesized and released by neurons which act on a site of action as a postsynaptic cell and are removed from this site. The neurotransmitters are aminoacid, amines, peptides and small molecules. We present different aspects of the phenotypic expression of molecules involved in the catecholaminergic and GABAergic neurotransmission in the developing human brain: these expressions can be observed either permanently during development and reflect the differentiation of a neuronal system or transiently at a restricted developmental stage and could correspond to a specific function on morphogenesis as neurogenesis, migration or differentiation processes.
Aminergic systems
1/ The catecholaminergic (dopamine, noradrenaline, adrenaline) neurons are detected by the presence of the synthetic enzyme, tyrosine hydroxylase around 5 postovulatory weeks of gestation in the human embryo. Tyrosine-hydroxylase immunoreactivity is observed in the postmitotic neurons of different cells groups as the substantia nigra or the locus ceruleus as they migrate and begin to differentiate. Similarly, the differentiation of the axonal field of these neurons can be observed in the basal ganglia and the cerebral cortex during fetal development in parallel with the detection of postsynaptic receptor sites.1
2/ Recently, we observed the transient immunocytochemical expression of the serotoninergic transporter SERT in fibers of the internal capsule in the human brain at 12-14 postovulatory week in humans. These fibers do not correspond to the ascending serotoninergic pathway running in the medial forebrain bundle. These findings could be correlated to data observed in rodents in which a transient expression of SERT in the thalamocortical axons seems to play an important role in the formation of the cortical sensory maps during the developmental critical period.2
GABAergic systems
In human embryon, germinal zones of the ganglionic eminence generate GABAergic neurons, subpopulations of local circuit neurons which migrate to the cortical anlage and the thalamus nuclei3,4. GABA-IR neurons are observed in the whole the ganglionic eminence particularly in the ventricular zone. GAD65 (one isoform of the synthetic enzyme for GABA)-immunoreactivity is restricted to the subventricular zone of the ganglionic eminence from 5 to 8 postovulatory weeks. During fetal life thalamic GABAergic local circuit neurons can be visualized by their GAD67-immunoreactivity at 16 g.w. 5
- Verney C,1999, Distribution of the Catecholaminergic neurons in the Central Nervous System of human embryos and fetuses, Micros Res Tech 46 :24-47.
- Verney C, Lebrand C, Gaspar P, 2002, Changing distribution of monoaminergic markers in the developing human cerebral cortex with special emphasis on the serotonin transporter. 2002. Anat Record, 267:87-93.
- Letinic K, Rakic P, 2001, Telencephalic origin of human thalamic GABAergic neurons, Nat Neuroscience 4:860-862.
- Letinic K, Zoncu R, RakicP, 2002, Origin of GABAergic neurons in the human cerebral cortex, Nature 417:605-607.
- Verney C, Fallet C, Danbold NC, Kultas-Ilinsky K. 2001 Early prenatal development of the motor-related subdivisions of human thalamus with special emphasis of GABAergic markers. Neurosci. Abstr. 31.
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