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Gobernado I.,Servicio de Psiquiatria | Sanchez-Herranz A.,Servicio de Neurobiologia Investigacion | Jimenez-Escrig A.,Servicio de Neurologia
Comprehensive Analytical Chemistry | Year: 2014

The development of parallel sequencing started a race with the aim to sequence massive amounts of DNA several orders of magnitude higher than the classical Sanger sequencing, providing the opportunity to screen large proportions of nucleic acids in a short time frame. This capability is no doubt the milestone of a new way to answer everyday questions in biology and medicine and represents a major field of research in the genomic field. This review focuses on the basic lines of next-generation sequencing, the practical approach to unravel the data generated and the diverse applications of these techniques to multiple fields in Biology and Medicine. © 2014 Elsevier B.V. Source


Knafo S.,Autonomous University of Madrid | Knafo S.,Technical University of Madrid | Venero C.,Spanish University for Distance Education (UNED) | Sanchez-Puelles C.,Autonomous University of Madrid | And 16 more authors.
PLoS Biology | Year: 2012

Cell adhesion molecules and downstream growth factor-dependent signaling are critical for brain development and synaptic plasticity, and they have been linked to cognitive function in adult animals. We have previously developed a mimetic peptide (FGL) from the neural cell adhesion molecule (NCAM) that enhances spatial learning and memory in rats. We have now investigated the cellular and molecular basis of this cognitive enhancement, using biochemical, morphological, electrophysiological, and behavioral analyses. We have found that FGL triggers a long-lasting enhancement of synaptic transmission in hippocampal CA1 neurons. This effect is mediated by a facilitated synaptic delivery of AMPA receptors, which is accompanied by enhanced NMDA receptor-dependent long-term potentiation (LTP). Both LTP and cognitive enhancement are mediated by an initial PKC activation, which is followed by persistent CaMKII activation. These results provide a mechanistic link between facilitation of AMPA receptor synaptic delivery and improved hippocampal-dependent learning, induced by a pharmacological cognitive enhancer. © 2012 Knafo et al. Source


Gonzalo-Gobernado R.,Servicio de Neurobiologia Investigacion | Calatrava-Ferreras L.,Servicio de Neurobiologia Investigacion | Perucho J.,Servicio de Neurobiologia Investigacion | Reimers D.,Servicio de Neurobiologia Investigacion | And 5 more authors.
Recent Patents on CNS Drug Discovery | Year: 2014

Liver growth factor (LGF) is a hepatic mitogen purified by our group in 1986. In the following years we demonstrated its activity both in “in vivo” and “in vitro” systems, stimulating hepatocytes mitogenesis as well as liver regeneration in several models of liver injury. Furthermore, we established its chemical composition (albumin-bilirubin complex) and its mitogenic actions in liver. From 2000 onwards we used LGF as a tissue regenerating factor in several models of extrahepatic diseases. The use of Liver growth factor as a neural tissue regenerator has been recently protected (Patent No US 2014/8,642,551 B2). LGF administration stimulates neurogenesis and neuron survival, promotes migration of newly generated neurons, and induces the outgrowth of striatal dopaminergic terminals in 6-hidroxydopamine-lesioned rats. Furthermore, LGF treatment raises striatal dopamine levels and protects dopaminergic neurons in hemiparkinsonian animals. LGF also stimulates survival of grafted foetal neural stem cells in the damaged striatum, reduces rotational behaviour and improves motor coordination. Interestingly, LGF also exerts a neuroprotective role both in an experimental model of cerebellar ataxia and in a model of Friedrich´s ataxia. Microglia seem to be the cellular target of LGF in the CNS. Moreover, the activity of the factor could be mediated by the stimulation of MAPK´s signalling pathway and by regulating critical proteins for cell survival, such as Bcl-2 and phospho-CREB. Since the factor shows neuroprotective and neurorestorative effects we propose LGF as a patented novel therapeutic tool that may be useful for the treatment of Parkinson´s disease and cerebellar ataxias. Currently, our studies have been extended to other neurological disorders such as Alzheimer’s disease (Patent No: US 2014/0113859 A1). © 2014 Bentham Science Publishers. Source


Albinana E.,Autonomous University of Madrid | Sacristan S.,Servicio de Neurobiologia Investigacion | Martin Del Rio R.,Servicio de Neurobiologia Investigacion | Solis J.M.,Servicio de Neurobiologia Investigacion | Hernandez-Guijo J.M.,Autonomous University of Madrid
Cellular and Molecular Neurobiology | Year: 2010

Taurine is one of the most abundant free amino acids in the central nervous system, where it displays several functions. However, its molecular targets remain unknown. It is well known that taurine can activate GABA-A and strychnine-sensitive glycine receptors, which increases a chloride conductance. In this study, we describe that acute application of taurine induces a dose-dependent inhibition of voltage-dependent calcium channels in chromaffin cells from bovine adrenal medullae. This taurine effect was not explained by the activation of either GABA-A, GABA-B or strychnine-sensitive glycine receptors. Interestingly, glycine mimicked the modulatory action exerted by taurine on calcium channels, although the acute application of glycine did not elicit any ionic current in these cells. Additionally, the modulation of calcium channels exerted by both taurine and glycine was prevented by the intracellular dialysis of GDP-β-S. Thus, the modulation of voltage-dependent calcium channels by taurine seems to be mediated by a metabotropic-like glycinergic receptor coupled to G-protein activation in a membrane delimited pathway. © 2010 Springer Science+Business Media, LLC. Source

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