Suchergebnisse

The generation of neurons in the adult mammalian brain requires the activation of quiescent neural stem cells (NSCs). This activation and the sequential steps of neuron formation from NSCs are regulated by a number of stimuli, which include growth factors. Insulin-like growth factor-I (IGF-I) exert pleiotropic effects, regulating multiple cellular processes depending on their concentration, cell type, and the developmental stage of the animal. Although IGF-I expression is relatively high in the embryonic brain its levels drop sharply in the adult brain except in neurogenic regions, i.e., the hippocampus (HP) and the subventricular zone-olfactory bulb (SVZ-OB). By contrast, the expression of IGF-IR remains relatively high in the brain irrespective of the age of the animal. Evidence indicates that IGF-I influences NSC proliferation and differentiation into neurons and glia as well as neuronal maturation including synapse formation. Furthermore, recent studies have shown that IGF-I not only promote adult neurogenesis by regulating NSC number and differentiation but also by influencing neuronal positioning and migration as described during SVZ-OB neurogenesis. In this article we will revise and discuss the actions reported for IGF-I signaling in a variety of in vitro and in vivo models, focusing on the maintenance and proliferation of NSCs/progenitors, neurogenesis, and neuron integration in synaptic circuits. ; The work in Carlos Vicario laboratory was funded by grants from the Spanish Ministerio de Ciencia e Innovación and Ministerio de Economía y Competitividad (MICINN and MINECO; BFU2007-61230, BFU2010-1963 and SAF2013-4759R, the Instituto de Salud Carlos III (ISCIII; CIBERNED CB06/05/0065), and the Comunidad de Madrid (S2011/BMD-2336) to CV. VN and ÇD were supported by a FPI Fellowship from the MICINN and MINECO and grants from CIBERNED and the European Union in the 7th framework program. ; Peer reviewed ; Peer Reviewed

Graphene, graphene-based nanomaterials (GBNs), and carbon nanotubes (CNTs) are being investigated as potential substrates for the growth of neural cells. However, in most in vitro studies, the cells were seeded on these materials coated with various proteins implying that the observed effects on the cells could not solely be attributed to the GBN and CNT properties. Here, we studied the biocompatibility of uncoated thermally reduced graphene (TRG) and poly(vinylidene fluoride) (PVDF) membranes loaded with multi-walled CNTs (MWCNTs) using neural stem cells isolated from the adult mouse olfactory bulb (termed aOBSCs). When aOBSCs were induced to differentiate on coverslips treated with TRG or control materials (polyethyleneimine-PEI and polyornithine plus fibronectin-PLO/F) in a serum-free medium, neurons, astrocytes, and oligodendrocytes were generated in all conditions, indicating that TRG permits the multi-lineage differentiation of aOBSCs. However, the total number of cells was reduced on both PEI and TRG. In a serum-containing medium, aOBSC-derived neurons and oligodendrocytes grown on TRG were more numerous than in controls; the neurons developed synaptic boutons and oligodendrocytes were more branched. In contrast, neurons growing on PVDF membranes had reduced neurite branching, and on MWCNTs-loaded membranes oligodendrocytes were lower in numbers than in controls. Overall, these findings indicate that uncoated TRG may be biocompatible with the generation, differentiation, and maturation of aOBSC-derived neurons and glial cells, implying a potential use for TRG to study functional neuronal networks. ; This work was funded by grants from the European Union in the 7th Framework Program research project "HARCANA" (Grant Agreement No. NMP3-LA-2008-213277) to CV-A, ML-M, VA, and CJ, and the Spanish Ministerio de Economía y Competitividad (MINECO: CIBERNED CB06/05/0065, SAF2013-47596R, and CSIC 201220E098) to CV-A, and MINECO (MAT2013-48107-C3) to RV, and from Millipore Iberica (Ref. no: 050601140007) to RM-M. CERM is grateful to IAP (7-05 FS2) and FRS-FNRS for financial support. ; Peer reviewed ; Peer Reviewed