Comparative gene expression profile of Hes1-overexpressing cultured hippocampal neurons vs the corresponding control populations (neurons expressing GFP)

Homologue of Enhancer-of-split 1 (Hes1) is a transcription factor that regulates neuronal plasticity, promoting the growth of dendrites and increasing the GABAergic input. A higher expression of Hes1 also results in neuronal resistance against the noxious activity of amyloid beta, the main agent in the advent and progression of the Alzheimer's disease. As a transcription factor, Hes1 controls de expression of many genes. Using the microarray technology we have detected that the expression of one secreted synaptic protein, cerebellin 4 (Cbln4) was particularly increased upon overexpression of Hes1. We also present evidence that Cbln4 plays an essential role in the formation and maintenance of inhibitory GABAergic connections and that either overexpression of Cbln4 in cultured hippocampal neurons or the application of recombinant Cbln4 to the cultures increased the number of GABAergic varicosities and rescued neurons from amyloid beta induced cell death.

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Chacón PJ, del Marco Á, Arévalo Á, Domínguez-Giménez P, García-Segura LM, Rodríguez-Tébar A