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Modulation de la migration neuronale par les neurotransmetteurs GABA et glutamate : aspects fondamentaux et implications pathologiques

Abstract : Recent advances in neuroimaging techniques have identified neuronal migration disorders as major causes of mental retardation, epilepsies and other neurological syndromes. Understanding the mechanisms modulating neuronal migration is then crucial to prevent such brain maturation disorders. Many studies have identified the neurotransmitters as early informative signals, acting before synapse formation, and influencing several aspects of CNS construction - i.e. neurogenesis, migration and differentiation. We have investigated the roles played by the transmitters GABA and glutamate during neuronal migration, as well as the consequences of the disturbance of their actions on foetal brain construction.
We have developed in vitro models to visualize migrating neurons - hippocampal pyramidal neurons and hippocampal interneurons. We have demonstrated that ambient GABA and glutamate, both released in a calcium and SNARE-independent manner, differentially modulate the migration of these two neuronal subtypes: GABAA and NMDA receptors activation modulate the radial migration of glutamatergic pyramidal neurons, whereas AMPA receptor activation modulates the tangential migration of GABAergic interneurons.
We have then investigated the impact of in utero exposure to antiepileptic drugs, which interfere with GABAergic and glutamatergic neurotransmission and modulate ionic channels. We report that prenatal exposure to vigabatrin and valproic acid (two drugs acting on the GABA system) induces hippocampal and cortical dysplasias in rats. These alterations of the foetal brain construction are suggestive of neuronal migration disorders and were observed at plasma drug concentrations within the range encountered clinically.
Altogether, these results suggest the presence of an early mode of communication through transmitters contributing to an appropriate brain construction and highlight the central role played by GABA and glutamate as major informative signals in developing brain. Our data also revealed the crucial need for evaluating the consequences of prenatal exposure to pharmacological agents interfering with transmitters actions during cerebral maturation.
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https://tel.archives-ouvertes.fr/tel-00103505
Contributor : Jean-Bernard Manent <>
Submitted on : Wednesday, October 4, 2006 - 3:31:01 PM
Last modification on : Friday, February 6, 2015 - 11:28:01 AM
Long-term archiving on: : Thursday, September 20, 2012 - 11:16:10 AM

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  • HAL Id : tel-00103505, version 1

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Jean-Bernard Manent. Modulation de la migration neuronale par les neurotransmetteurs GABA et glutamate : aspects fondamentaux et implications pathologiques. Neurosciences [q-bio.NC]. Université de la Méditerranée - Aix-Marseille II, 2006. Français. ⟨tel-00103505v1⟩

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