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Título

Glycogen synthase kinase 3 inhibitors promote adult hippocampal neurogenesis

Autor Morales-García, José A. ; Palomo Ruiz, Valle; Gil, Carmen ; Martínez, Ana ; Santos, Ángel; Pérez Castillo, Ana
Fecha de publicación 2011
EditorAlzheimer’s Association
Citación ICAD 2011
Resumen[Background]: In the central nervous system, developing neurons are derived from quiescent multipotent or neural stem cells. Throughout life, neural progenitors in the sub ventricular zone of the lateral ventricles and the sub-granular zone of the dentate gyrus of the hippocampus give rise to interneurons of the olfactory bulb and neurons of the granule cell layer of the dentate gyrus. Glycogen synthase kinase-3 beta (GSK-3beta) is a serine/threonine kinase originally identified as a regulator of glycogen metabolism but it also plays a pivotal role in numerous cellular functions. Considering the important role of GSK-3beta in neuroprotection and its role in regulating neuronal differentiation, we speculated that this enzyme could have a role in hippocampal stem/progenitor cells. [Methods]: We have used an in vitro approach using neurosphere cultures isolated from rat hippocampus to analyze the role of different GSK-3 beta inhibitors upon growth, migration of cells out of the neurospheres and differentiation towards a neuronal phenotype. We have also studied the effect of GSK-3 beta inhibition in in vivo neurogenesis by analyzing neuroblasts formation in the hippocampus of adult rats. [Results]: Our studies showed that inhibitors of GSK-3 beta are potent inducers of neuroblasts formation in the subgranularzone of the dentate gyrus of the hippocampus (one of the regions in which neurogenesis takes place in the adult brain) of adult rats. Also, in vitro studies demonstrate that inhibition of GSK-3 beta induces proliferation, migration, and differentiation of neural stem cells towards a neuronal phenotype. [Conclusions]: Our studies showed that inhibitors of GSK-3 beta are potent inducers of neuroblasts formation in the sub granular zone of the dentate gyrus of the hippocampus (one of the regions in which neurogenesis takes place in the adult brain) of adult rats. Also, in vitro studies demonstrate that inhibition of GSK-3 beta induces proliferation, migration, and differentiation of neural stem cells towards a neuronal phenotype.
Descripción Póster presentado a la "Alzheimer's Association International Conference" celebrada del 16 al 21 de julio de 2011 en Paris (Francia)..-- Publicado resumen en: Alzheimer's and Dementia 7(4,Supl.): S662-S663 (2011) de Elsevier con DOI: 10.1016/j.jalz.2011.05.1903
URI http://hdl.handle.net/10261/102108
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