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Synaptogenèses normales, pathologiques et amendables dans le cortex cérébral

Normal, pathological and mendable synaptogenesis in the cerebral cortex

  • Neurosciences / Neurosciences
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Résumé

Dans le cortex cérébral, les diverses phases des synaptogenèses coïncident avec les étapes majeures des maturations des fonctions sensorielles, motrices et cognitives. L’évolution du cortex cérébral, pendant 300 millions d’années, a sélectionné des réseaux de gènes contrôlant le développement robuste des réseaux synaptiques, tout en permettant à l’environnement de les raffiner en permanence, dans une fenêtre de variabilité elle-même contrôlée génétiquement. L’inscription épigénétique permanente de l’histoire de l’individu dans l’affinage final de ses circuits synaptiques dure toute la vie, avec un effet maximum pendant les périodes critiques du développement. Cette « ouverture épigénétique » de l’histoire individuelle, maximale dans le cortex humain, est la source de la très grande créativité cognitive et culturelle de notre espèce, et peut-être aussi de ses fragilités psychiques. Le séquençage et l’analyse du génome humain montrent que des ensembles de mutations affectant les voies de signalisations synaptiques sont associés à des maladies psychiatriques. Les neurobiologistes savent manipuler l’ouverture et la fermeture des périodes critiques de synaptogenèse au cours du développement et commencent à le faire aussi dans le cortex cérébral adulte. Ces manipulations épigénétiques des synapses pourront-elles « réparer » les circuits synaptiques pathologiquement altérés?

Abstract

In the cerebral cortex, different phases of synaptogenesis coincide with the main maturation stages of sensory, motor, and cognitive abilities. Early in development, synapses are generated and differentiated under the control of robust mechanisms governed by genes. Then, during multiple critical periods, extending from the end of gestation to the end of puberty, the way in which the synaptic structure develops is highly dependent upon the quality of the environment. The duration of these critical periods increases significantly through evolution. This “epigenetic opening” of synaptogenesis to the environment is maximal in the human cerebral cortex. It is the source of the exceptional cognitive adaptability and cultural creativity of our species. It is also, possibly, one of our multiple psychological fragilities. Analysis of the human genome reveals that mutations in genes related to synaptic structure and signalisation are linked to many psychiatric disorders. Neurobiologists are able to manipulate the critical periods of synaptogenesis during development and have begun to do so in the adult cerebral cortex. These epigenetic manipulations might allow us to restore synaptic plasticity and, potentially, repair the disorganised synaptic circuits observed in psychiatric pathologies. You said epigenetic manipulations?

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  1. CNRS URA2182 « Gène, synapse et cognition », laboratoire de génétique humaine et fonctions cognitives, département des neurosciences, Institut Pasteur, 25, rue du Docteur-Roux, F-75724, Paris cedex 15, France

    J. -P. Bourgeois

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Bourgeois, J.P. Synaptogenèses normales, pathologiques et amendables dans le cortex cérébral. Psychiatr Sci Hum Neurosci 6, 124–136 (2008). https://doi.org/10.1007/s11836-008-0065-z

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