MECHANISMS OF NEURONAL MAINTENANCE

Our group´s work is focused on two main topics:

    i) Elucidation of the mechanisms underlying the positive effects of trophic factors on specific neuronal populations. In particular, we are characterizing the molecular players involved in the maintenance by GDNF of specific catecholaminergic populations in the central and the peripheral nervous system. By using genetically modified animals, proteomic, genomic and imaging techniques we are identifying neuroprotective actions of the trophic factors that operate both at the level of the terminals and the soma of these neurons.

    ii) We are also studying neuronal adaptations to acute decrease in the levels of the available oxygen. These mechanisms will be crucial in determining cellular fate after an hypoxic or ischemic insult. We have used proteomics techniques to study how the proteome evolves in cellular lines and in animals to respond to a physiologically brief episode of hypoxia. The underlying hypothesis is that all cells, and in particular neurons, have specific acute molecular responses to achieve homeostasis under oxygen deprivation.

Keywords:

    Trophic factors, neruodegenerative diseases, Parkinson´s disease, GDNF, proteomics, genomics, genetically modified animals, hypoxia, ischemia

            Pascual, A. and Vioque, A. (1994) Sequence and structure of the RNA subunit of RNase P from the cyanobacterium Pseudanabaena sp. PCC6903. Biochim. Biophys. Acta, 1218: 463-465.

            Pascual, A. and Vioque, A. (1996) Cloning, purification and characterization of the protein subunit of ribonuclease P from the cyanobacterium Synechocystis sp. PCC6803. Eur. J. Biochem., 241: 17-24.

            Peciña, A., Pascual, A. & Paneque, A. (1999) Cloning and expression of the algL gene, encoding the Azotobacter chroococcum alginate lyase: purification and characterization of the enzyme. J. Bacteriol., 181: 1409-14.

            Pascual A. and Vioque A (1999) Functional reconstitution of RNase P activity from a plastid RNA subunit and a cyanobacterial protein subunit. FEBS Lett., 442: 7-10.

            Pascual A., Vioque A. (1999) Substrate binding and catalysis by ribonuclease P from cyanobacteria and Escherichia coli are affected differently by the 3´-terminal CCA in tRNA precursors. Proc. Natl. Acad. Sci. USA, 96: 6672-6677.

            Pascual, A., Préat T. (2001) Localization of long-term memory within the Drosophila mushroom body. Science, 294: 1115-1117.

            Pascual, A., Huang, K.-L., Neveau, J., Préat T. (2004) Neuroanatomy: brain asymmetry and long-term memory. Nature, 427: 605-606.

            Isabel, G.*, Pascual, A.*, Préat T. (2004) Exclusive consolidated memory phases in Drosophila. Science, 304: 1024-1027. (*) These authors contributed equally to this work.

            Pascual, A.*, Chaminade, M.* and Preat, T.. (2005) Ethanolamine kinase controls neuroblast division in Drosophila mushroom bodies. Dev. Biol., 280: 177-186. (*) These authors contributed equally to this work.

            Pascual, A., Huang, K.-L., and Preat, T. (2005) Conditional UAS-targeted repression in Drosophila. Nucleic Acids Res., 33: e7.

            Ortega-Saenz, P.*, Pascual, A.*, Gomez-Diaz, R. and Lopez-Barneo, J. (2006) Acute Oxygen Sensing in Heme Oxygenase-2 Null Mice. J. Gen. Physiol., 128: 405-411. (*) These authors contributed equally to this work. Cover article.

            Ortega-Sáenz, P., Pascual, A., Piruat, J.I. and López-Barneo, J. (2007) Mechanisms of acute oxygen sensing: lessons from genetically modified animals. Respir. Physiol. Neurobiol. 157: 140-147.

           Bishop, T., Gallagher, D., Pascual, A., Lygate, C. A., de Bono, J. P., Wijeyekoon, B., Ortega-Saenz, P. O., Oster, H., Nicholls, L. G., Teixeira, D., Lopez-Barneo, J., Channon, K. M., Maxwell, P. H., Pugh, C. W., Davies, A. M., Carmeliet, P., and Ratcliffe, P. J. (2008) Dysfunctional hyperplasia of sympatho-adrenal tissues and systemic hypotension in PHD3-/- mice. Mol. Cell. Biol. 28: 3386-400.

            López-Barneo, J., Ortega-Sáenz, P., Pardal, R., Pascual, A., and Piruat, J. I. (2008) Carotid Body Oxygen Sensing. Eur. Res. Physiol. 32: 1386-98.

            Pascual, A.*, Hidalgo-Figueroa, M.*, Piruat, J.I., Pintado, C. O., Gomez-Diaz R., and López-Barneo, J. (2008) Absolute Requirement of GDNF for Adult Catecholaminergic Neuron Survival. Nature Neuroscience. 11: 755-761. (*) These authors contributed equally to this work.

            Pascual, A.*, Romero-Ruiz, A. and López-Barneo, J. (2009) Differential proteomic analysis of adrenal gland during postnatal development. Proteomics. 9: 2946-2954. (*) Corresponding author.

           López-Barneo, J., Ortega-Sáenz, P., Pardal, R., Pascual, A., Piruat, J.I., Durán, R., y Gómez-Díaz, R. (2009) Oxygen sensing in the carotid body. Annals of the New York Academy of Sciences. 1177: 119-131.

Protemics (DIGE, 2DE)

Histology

Genetically modified animals  

Drosophila