In this study, we first aimed at "rejuvenation" by forcibly expressing genes that are highly expressed in the embryonic period, in which neural stem cells actively proliferate and produce many neurons, in neural stem cells of aged mice.As a result, it was found that forced expression of the zinc finger protein Plagl2 can activate aging neurons most strongly.

　Next, when we attempted to activate neural stem cells in aged mice by combining forced expression of Plagl2 and knockdown of genes that are highly expressed in old age, knockdown of Down's syndrome-related kinase Dyrk1a was the most efficient method for aging neural stem cells. It was found to activate proliferative and neuronal producing abilities.Aging neural stem cells, which had almost completely lost their ability to proliferate and produce neurons, are said to have revived to the same level as in their youth by this combination.The rejuvenated neural stem cells continued to grow for at least 3 months and produced a large number of neurons.

　The research group named the combination of forced expression of Plagl2 and knockdown of Dyrk1a as iPaD (inducing Plagl2 and anti-Dyrk1a). In aged mice treated with iPaD, improvement in cognitive function was observed in tests examining spatial memory and cognitive memory. iPaD alters the chromatin structure of neural stem cells, reducing the expression of genes that work in old age and increasing the expression of genes that work in embryonic period, that is, the reversal phenomenon between the gene expression pattern in old age and the gene expression pattern in young age. It is said that it was induced.

　The results of this research, which showed that neural stem cells in old age can be rejuvenated to produce neurons and improve cognitive function, are expected to lead to the development of new treatments for dementia.

Paper information:[Genes & Development] Functional rejuvenation of aged neural stem cells by Plagl2 and anti-Dyrk1a activity