Induction de la différenciation neuronale par deux polyphénols présents dans le régime méditerranéen : le resvératrol et l'apigénine

Résumé 0

To prevent neurodegeneration associated to aging or observed in numerous neurodegenerative diseases, it can be of interest to favor neuronal differentiation of immature and pluripotent stem cells. ODN, produced by astrocytes, is an endozepine generated through the proteolytic cleavage of the diazepam binding inhibitor (DBI). ODN stimulates neurogenesis in the adult mouse brain and prevents apoptosis associated with oxidative stress. Retinoic acid (RA) triggers the differentiation of numerous cell types, including nerve cells. Apigenin (API), present in parsley, rosemary, and honey, promotes the differentiation of B104 rat neuronal cells. Resveratrol (RSV), a major compound found in red wine, activates neuronal differentiation of human bone marrow mesenchymal stem cells via SIRT1. RA, API and RSV cross the blood brain barrier. In the context of neuroprotection, it is therefore of interest to compare the differentiating capacities and the toxicity of these molecules. The most relevant molecules will be the one strongly inducing differentiation with no cytotoxic side effects. To this end, murine neuronal N2a cells were used and cultured with different concentrations of ODN (10-16M – 10-8M), retinoic acid (RA: 6.25µM-50µM), resveratrol (RSV: 6.25µM-50µM) and API (6.25µM-50µM) for 48 h without or with 10% fetal bovine serum (FBS). Neuronal differentiation was morphologically (presence of dendrites and axons) and cytologically (presence of Nissl bodies) evaluated. Cell viability was determined by staining with fluoresceine diacetate (FDA). The presence of metabolically active axons was evaluated by Mitotracker staining. Neuronal differentiation was much more efficient in the absence of serum (AR (61%) > ODN (37%) ≥ RSV (37%) > API (33%)). At concentrations inducing differentiation, no cytotoxicity was observed for ODN or RSV, API was slightly toxic, RA induces a marked cytotoxicity. For ODN, metabolically active neurons were observed. Thus, polyphenols present in the Mediterranean diet (RSV, API) could contribute to prevent neurodegeneration and are therefore of high interest in regenerative medicine.