80 results on '"Aguado T"'
Search Results
2. THE ENDOCANNABINOID SYSTEM AND THE REGULATION OF NEUROGENESIS: YIC05-03
- Author
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Galve-Roperh, I., Aguado, T., Palazuelos, J., Díaz, J., and Guzm´n, M.
- Published
- 2009
3. Multifunctional albumin-stabilized gold nanoclusters for the reduction of cancer stem cells
- Author
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Latorre A., Latorre A., Castellanos M., Diaz C.R., Lazaro-Carrillo A., Aguado T., Lecea M., Romero-Pérez S., Calero M., Sanchez-Puelles J.M., Villanueva Á., Somoza Á. and Funding: This research was funded by the Spanish Ministry of Economy and Competitiveness (CTQ2016-78454-C2-2-R, SAF2014-56763-R, and SAF2017-87305-R), Comunidad de Madrid (S2013/MIT-2850), Asociación Española Contra el Cáncer, and IMDEA Nanociencia IMDEA Nanociencia acknowledges support from the ‘Severo Ochoa’ Programme for Centres of Excellence in R&D (MINECO, Grant SEV-2016-0686).
- Published
- 2019
4. Cannabinoid inhibition of neuronal differentiation
- Author
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Galve-Roperh, I., Rueda, D., Navarro, B., Aguado, T., Martínez-Serrano, A., and Guzmaán, M.
- Published
- 2003
5. 631 Oxidative stress imbalance as contributing factor in the establishment of fibrosis in recessive dystrophic epidermolysis bullosa
- Author
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Chacón-Solano, E., primary, Aguado, T., additional, Sánchez-Domínguez, R., additional, León, C., additional, Carretero, M., additional, Escámez, M., additional, Ruiz-Mezcua, B., additional, Sánchez-Puelles, J., additional, Larcher, F., additional, and del Río, M., additional
- Published
- 2019
- Full Text
- View/download PDF
6. Endocannabinoid signaling controls pyramidal cell specification and long-range axon patterning
- Author
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Mulder J, Aguado T, Keimpema E, Barabás K, Ballester Rosado CJ, Nguyen L, Monory K, Marsicano G, Di Marzo V, Hurd YL, Guillemot F, Mackie K, Lutz B, Guzmán M, Lu HC, Galve-Roperh I, and Harkany T.
- Published
- 2008
7. Racismo, adolescencia e inmigración : reconocer y afrontar el racismo desde una perspectiva educativa
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Mata, P., Aguado, T., Ballesteros, B., Gil Jaurena, I., Hernández Sánchez, Caridad, Luque, C., Malik, B., Olmo, M. del, Téllez, J. A., and Universidad Nacional de Educación a Distancia (Espanya). Centro INTER de Investigación en Educación Intercultural
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Immigració ,Racisme ,Inmigración ,Educación intercultural ,Racismo ,Educació intercultural - Abstract
Este texto se presentó como comunicación al II Congreso Internacional de Etnografía y Educación: Migraciones y Ciudadanías. Universidad Autónoma de Barcelona, Barcelona, 5-8 Septiembre 2008. El racismo es una realidad compleja que, pese a estar presente en nuestra experiencia cotidiana, tanto dentro como fuera de los centros educativos, suele, sin embargo, ignorarse o negarse. Por ello, no resulta fácil hablar de racismo. Partiendo de esta reflexión nos planteamos en este proyecto acercarnos a las percepciones y experiencias de los adolescentes en torno a este fenómeno, a sus manifestaciones sutiles o explícitas, a sus implicaciones y consecuencias. Nuestra intención era tratar de comprender el fenómeno del racismo desde el punto de vista de los afectados, lo que implica básicamente: • Conocer la percepción de los jóvenes en relación con experiencias/situaciones de racismo. • Reconocer el racismo implícito en situaciones cotidianas, dentro y fuera del ámbito educativo. • Apreciar las dificultades con las que se encuentran jóvenes de diversos orígenes en su vida fuera y dentro del medio escolar. Pretendíamos dar voz a los chicos y chicas que viven, sufren o afrontan el racismo, con la finalidad de obtener información relevante para elaborar una Guía, dirigida al profesorado y adultos en general, y también a los propios adolescentes, que les ayudara a reconocer, comprender, interpretar y manejar situaciones de racismo desde una perspectiva educativa. Para ello contactamos con adolescentes cuyas características nos hicieron prejuzgar que podían formar parte de grupos que sufren cotidianamente el peso del racismo: sobre todo, chicas y chicos a los que solemos asociar con la categoría de «inmigrante». Los abordamos no sólo en los centros educativos, sino también en las calles y en los parques, allí donde pensamos que podían compartir sus ideas y experiencias en un clima de confianza. Descubrimos que los adolescentes tienen una visión clara y amplia del racismo y sus implicaciones, y son capaces de distinguir y narrar sus experiencias en torno a él. Así mismo, reclaman que se hable de racismo, que se trate abiertamente, que sus vivencias y percepciones se tengan en cuenta y reciban algún tipo de respuesta por parte de los adultos. Tomando como referente esta idea, construimos una Guía articulada en torno a sus narraciones, que trata de ofrecer ideas y propuestas que respondan a cinco cuestiones: qué es el racismo, por qué y para qué se da, cómo se produce, cómo se reproduce y cómo se afronta.
- Published
- 2007
8. HPV vaccine use in the developing world
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Kane, MA, Sherris, J, Coursaget P Aguado, T, Cutts, F, and Inconnu
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[SDV]Life Sciences [q-bio] - Published
- 2006
9. Phylogeny of Sabellidae (Annelida) and relationships with other taxa inferred from morphology and multiple genes (project)
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Capa, C, primary, Hutchings, H, additional, Aguado, T, additional, and Bott, J, additional
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- 2014
- Full Text
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10. Phylogeny of Sabellidae (Annelida) and relationships with other taxa inferred from morphology and multiple genes [X1426] (matrix)
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Capa, C, primary, Hutchings, H, additional, Aguado, T, additional, and Bott, J, additional
- Published
- 2014
- Full Text
- View/download PDF
11. The CB1 Cannabinoid Receptor Drives Corticospinal Motor Neuron Differentiation through the Ctip2/Satb2 Transcriptional Regulation Axis
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Diaz-Alonso, J., primary, Aguado, T., additional, Wu, C.-S., additional, Palazuelos, J., additional, Hofmann, C., additional, Garcez, P., additional, Guillemot, F., additional, Lu, H.-C., additional, Lutz, B., additional, Guzman, M., additional, and Galve-Roperh, I., additional
- Published
- 2012
- Full Text
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12. [P2.61]: CB 1 cannabinoid receptors regulate pyramidal neuron layer specification
- Author
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Díaz, J., primary, Aguado, T., additional, Palazuelos, J., additional, Rosado‐Ballester, C., additional, Lutz, B., additional, and Lu, H.C., additional
- Published
- 2010
- Full Text
- View/download PDF
13. Focus: Meningococcal meningitis
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Aguado, T., primary, Bertherat, E., additional, Djingarey, M., additional, Kandolo, D., additional, Kieny, M. P., additional, Kondé, K., additional, LaForce, F. M., additional, Nelson, C. B., additional, Perea, W., additional, and Préziosi, M. P., additional
- Published
- 2005
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14. Comparison of HPV type distribution in high-grade cervical lesions and cervical cancer: a meta-analysis
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Clifford, G M, primary, Smith, J S, additional, Aguado, T, additional, and Franceschi, S, additional
- Published
- 2003
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15. Loss of striatal type 1 cannabinoid receptors is a key pathogenic factor in Huntington's disease.
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Blázquez C, Chiarlone A, Sagredo O, Aguado T, Pazos MR, Resel E, Palazuelos J, Julien B, Salazar M, Börner C, Benito C, Carrasco C, Diez-Zaera M, Paoletti P, Díaz-Hernández M, Ruiz C, Sendtner M, Lucas JJ, de Yébenes JG, and Marsicano G
- Published
- 2011
- Full Text
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16. Effect of autologous and homologous serum and circulating immune complexes on monocyte functions of patients with solid tumours
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Antonio Celada, Aguado, T., Lambert, P. H., and Cruchaud, A.
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Male ,Blood Bactericidal Activity ,Chemotaxis, Leukocyte ,Phagocytosis ,Neoplasms ,Humans ,Female ,Antigen-Antibody Complex ,Complement System Proteins ,Middle Aged ,Monocytes ,Research Article ,Aged - Abstract
Some functions of monocytes (phagocytosis, bactericidal capacity, handling of endocytosed 51Cr-SRBC and chemotaxis) were studied in fifty patients with solid tumours and in fifty controls. In the presence of autologous serum, the catabolism of endocytosed 51Cr-SRBC and the phagocytic capacity were similar in tumour and control monocytes, while the bactericidal capacity of tumour monocytes was increased. In the presence of pooled AB sera the catabolism and the bactericidal capacity were decreased in tumour monocytes as compared with autologous serum. Tumour sera did not enhance the functions of normal monocytes. Inactivation of pooled tumour or AB sera resulted in decrease of bactericidal capacity in tumour and control monocytes. Using the Clq-binding test, we detected circulating immune complexes in 36% of sera. The presence or absence and the quantity of such complexes did not correlate with the different functions studied in either tumour or normal monocytes. Finally, the chemotactic activity of monocytes was studied using the migration under agarose technique. No difference was found between tumour and control monocytes. On the other hand, the presence of a chemotactic inhibitor was not revealed in tumour sera. These observations suggest that monocytes from tumour patients require factor(s) present in autologous serum as well as autologous cellular component(s) to achieve normal functions.
- Published
- 1980
17. Observation of Cosmic Ray Anisotropy with Nine Years of IceCube Data
- Author
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Mcnally, F., Abbasi, R., Desiati, P., Vélez, J. C. D., Aguado, T., Gruchot, K., Moy, A., Simmons, A., Thorpe, A., Woodward, H., Ackermann, M., Adams, J., Aguilar, J. A., Ahlers, M., Ahrens, M., Alispach, C., Alves, A. A., Amin, N. M., An, R., Andeen, K., Anderson, T., Anton, G., Argüelles, C., Ashida, Y., Axani, S., Bai, X., Balagopal, A. V., Barbano, A., Barwick, S. W., Bastian, B., Basu, V., Baur, S., Bay, R., Beatty, J. J., Becker, K. -H, Becker Tjus, J., Bellenghi, C., Benzvi, S., Berley, D., Bernardini, E., Besson, D. Z., Binder, G., Bindig, D., Blaufuss, E., Blot, S., Boddenberg, M., Bontempo, F., Borowka, J., Böser, S., Botner, O., Böttcher, J., Bourbeau, E., Bradascio, F., Braun, J., Bron, S., Brostean-Kaiser, J., Browne, S., Burgman, A., Burley, R. T., Busse, R. S., Campana, M. A., Carnie-Bronca, E. G., Chen, C., Chirkin, D., Choi, K., Clark, B. A., Clark, K., Classen, L., Coleman, A., Collin, G. H., Conrad, J. M., Coppin, P., Correa, P., Cowen, D. F., Cross, R., Dappen, C., Dave, P., Clercq, C., Delaunay, J. J., Dembinski, H., Deoskar, K., Ridder, S., Desai, A., Vries, K. D., Wasseige, G., With, M., Deyoung, T., Dharani, S., Diaz, A., Díaz-Vélez, J. C., Dittmer, M., Dujmovic, H., Dunkman, M., Duvernois, M. A., Dvorak, E., Ehrhardt, T., Eller, P., Engel, R., Erpenbeck, H., Evans, J., Evenson, P. A., Fan, K. L., Fazely, A. R., Fiedlschuster, S., Fienberg, A. T., Filimonov, K., Finley, C., Fischer, L., Fox, D., Franckowiak, A., Friedman, E., Fritz, A., Fürst, P., Gaisser, T. K., Gallagher, J., Ganster, E., Garcia, A., Garrappa, S., Gerhardt, L., Ghadimi, A., Glaser, C., Glauch, T., Glüsenkamp, T., Goldschmidt, A., Gonzalez, J. G., Goswami, S., Grant, D., Grégoire, T., Griswold, S., Gündüz, M., Günther, C., Haack, C., Hallgren, A., Halliday, R., Halve, L., Halzen, F., Ha Minh, M., Hanson, K., Hardin, J., Harnisch, A. A., Haungs, A., Hauser, S., Hebecker, D., Helbing, K., Henningsen, F., Hettinger, E. C., Hickford, S., Hignight, J., Hill, C., Hill, G. C., Hoffman, K. D., Hoffmann, R., Hoinka, T., Hokanson-Fasig, B., Hoshina, K., Huang, F., Huber, M., Huber, T., Hultqvist, K., Hünnefeld, M., Hussain, R., In, S., Iovine, N., Ishihara, A., Jansson, M., Japaridze, G. S., Jeong, M., Jones, B. J. P., Kang, D., Kang, W., Kang, X., Kappes, A., Kappesser, D., Karg, T., Karl, M., Karle, A., Katz, U., Kauer, M., Kellermann, M., Kelley, J. L., Kheirandish, A., Kin, K., Kintscher, T., Kiryluk, J., Klein, S. R., Koirala, R., Kolanoski, H., Kontrimas, T., Köpke, L., Kopper, C., Kopper, S., Koskinen, D. J., Koundal, P., Kovacevich, M., Kowalski, M., Kozynets, T., Kun, E., Kurahashi, N., Lad, N., Lagunas Gualda, C., Lanfranchi, J. L., Larson, M. J., Lauber, F., Lazar, J. P., Lee, J. W., Leonard, K., Leszczyńska, A., Li, Y., Lincetto, M., Liu, Q. R., Liubarska, M., Lohfink, E., Lozano Mariscal, C. J., Lu, L., Lucarelli, F., Ludwig, A., Luszczak, W., Lyu, Y., Ma, W. Y., Madsen, J., Mahn, K. B. M., Makino, Y., Mancina, S., Mariş, I. C., Maruyama, R., Mase, K., Mcelroy, T., Mead, J. V., Meagher, K., Medina, A., Meier, M., Meighen-Berger, S., Micallef, J., Mockler, D., Teresa Montaruli, Moore, R. W., Morse, R., Moulai, M., Naab, R., Nagai, R., Naumann, U., Necker, J., Nguyên, L. V., Niederhausen, H., Nisa, M. U., Nowicki, S. C., Nygren, D. R., Obertacke Pollmann, A., Oehler, M., Olivas, A., O’sullivan, E., Pandya, H., Pankova, D. V., Park, N., Parker, G. K., Paudel, E. N., Paul, L., Pérez Los Heros, C., Peters, L., Peterson, J., Philippen, S., Pieloth, D., Pieper, S., Pittermann, M., Pizzuto, A., Plum, M., Popovych, Y., Porcelli, A., Prado Rodriguez, M., Price, P. B., Pries, B., Przybylski, G. T., Raab, C., Raissi, A., Rameez, M., Rawlins, K., Rea, I. C., Rehman, A., Reichherzer, P., Reimann, R., Renzi, G., Resconi, E., Reusch, S., Rhode, W., Richman, M., Riedel, B., Roberts, E. J., Robertson, S., Roellinghoff, G., Rongen, M., Rott, C., Ruhe, T., Ryckbosch, D., Rysewyk Cantu, D., Safa, I., Saffer, J., Sanchez Herrera, S. E., Sandrock, A., Sandroos, J., Santander, M., Sarkar, S., Satalecka, K., Scharf, M., Schaufel, M., Schieler, H., Schindler, S., Schlunder, P., Schmidt, T., Schneider, A., Schneider, J., Schröder, F. G., Schumacher, L., Schwefer, G., Sclafani, S., Seckel, D., Seunarine, S., Sharma, A., Shefali, S., Silva, M., Skrzypek, B., Smithers, B., Snihur, R., Soedingrekso, J., Soldin, D., Spannfellner, C., Spiczak, G. M., Spiering, C., Stachurska, J., Stamatikos, M., Stanev, T., Stein, R., Stettner, J., Steuer, A., Stezelberger, T., Stürwald, T., Stuttard, T., Sullivan, G. W., Taboada, I., Tenholt, F., Ter-Antonyan, S., Tilav, S., Tischbein, F., Tollefson, K., Tomankova, L., Tönnis, C., Toscano, S., Tosi, D., Trettin, A., Tselengidou, M., Tung, C. F., Turcati, A., Turcotte, R., Turley, C. F., Twagirayezu, J. P., Ty, B., Unland Elorrieta, M. A., Valtonen-Mattila, N., Vandenbroucke, J., Eijndhoven, N., Vannerom, D., Santen, J., Verpoest, S., Vraeghe, M., Walck, C., Watson, T. B., Weaver, C., Weigel, P., Weindl, A., Weiss, M. J., Weldert, J., Wendt, C., Werthebach, J., Weyrauch, M., Whitehorn, N., Wiebusch, C. H., Williams, D. R., Wolf, M., Woschnagg, K., Wrede, G., Wulff, J., Xu, X. W., Xu, Y., Yanez, J. P., Yoshida, S., Yu, S., Yuan, T., and Zhang, Z.
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Astrophysics::High Energy Astrophysical Phenomena ,cosmic radiation: energy ,energy resolution ,Scale (descriptive set theory) ,Cosmic ray ,Astrophysics ,power spectrum ,anisotropy [cosmic radiation] ,UHE ,cosmic radiation: anisotropy ,IceCube ,energy dependence ,energy [cosmic radiation] ,Observatory ,muon ,optical ,Range (statistics) ,ddc:530 ,structure ,Anisotropy ,Muon ,background ,Physics ,Astrophysics::Instrumentation and Methods for Astrophysics ,stability ,sensitivity ,solar ,observatory ,Data set ,CERN LHC Coll ,statistics ,time dependence ,Event (particle physics) ,Geology - Abstract
37th International Cosmic Ray Conference, ICRC 2021, Berlin, Germany, 15 Jul 2021 - 22 Jul 2021; Proceedings of Science 395, 320 (2022). doi:10.22323/1.395.0320 special issue: "37th International Cosmic Ray Conference : ICRC2021 : 12-23 July 2021 : Berlin, Germany - Online / Editorial Board: Alexander Kappes, Institut für Kernphysik, Westfälische Wilhelms-Universität Münster, D-48149 Münster, Germany ; Bianca Keilhauer, Karlsruhe Institute of Technology, Institute for Astroparticle Physics (IAP)", Published by SISSA, Trieste
18. Telomere length defines the cardiomyocyte differentiation potency of mouse induced pluripotent stem cells
- Author
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Aguado T, Fj, Gutiérrez, Aix E, Rp, Schneider, Giovinnazo G, Maria A. Blasco, and Flores I
19. The CB1 cannabinoid receptor mediates excitotoxicity-induced neural progenitor proliferation and neurogenesis (Journal of Biological Chemistry (2007) 282, (23892-23898))
- Author
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Aguado, T., Romero, E., Monory, K., Palazuelos, J., Sendtner, M., Giovanni Marsicano, Lutz, B., Guzmán, M., and Galve-Roperh, I.
20. Circulating Immune Complexes in Patients with Haemophilia and von Willebrand’s Disease
- Author
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Aguado, T., primary, Celada, A., additional, Ortega, F., additional, Magallon, M., additional, Martin-Villar, J., additional, and Lambert, P.H., additional
- Published
- 1981
- Full Text
- View/download PDF
21. CB1 cannabinoid receptors regulate pyramidal neuron layer specification
- Author
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Díaz, J., Aguado, T., Palazuelos, J., Rosado-Ballester, C., Lutz, B., and Lu, H.C.
- Published
- 2010
- Full Text
- View/download PDF
22. Circulating Immune Complexes in Patients with Haemophilia and von Willebrand’s Disease
- Author
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Aguado, T., Celada, A., Ortega, F., Magallon, M., Martin-Villar, J., and Lambert, P.H.
- Published
- 1981
- Full Text
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23. Meningococcal conjugate vaccine for Africa: a model for development of new vaccines for the poorest countries.
- Author
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Jódar L, LaForce FM, Ceccarini C, Aguado T, and Granoff DM
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- 2003
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24. The real cost of an affordable vaccine for meningococcus A.
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Rappuoli R, LaForce FM, Granoff D, Jodar L, Ceccarini C, and Aguado T
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- 2003
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25. Una querida andaluza
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Roll, Hipólito, Kock, Paul de, and Aguado, T., (Madrid)
- Abstract
Hipólito Roll es seudónimo de Louis Reybaud. También usó los seudónimos de Paul Clisson y Jerôme Paturot 1-44(8), t. 4. : 223p. - En la misma pág. : Una querida andaluza por Paul de Kock ; versión de D. Eugenio González de Aposua
- Published
- 1844
26. Gerónimo Paturot en busca de una posición social
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Roll, Hipólito, Kock, Paul de, and Aguado, T., (Madrid)
- Abstract
Hipólito Roll es seudónimo de Louis Reybaud. También usó los seudónimos de Paul Clisson y Jerôme Paturot 1-44(8), t. 4. : 223p. - En la misma pág. : Una querida andaluza por Paul de Kock ; versión de D. Eugenio González de Aposua
- Published
- 1844
27. Cannabinoid CB 1 receptor expression in oligodendrocyte progenitors of the hippocampus revealed by the NG2-EYFP-knockin mouse.
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Manterola A, Chara JC, Aguado T, Palazuelos J, Matute C, and Mato S
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Adult oligodendrocyte progenitor cells (OPCs) give rise to myelinating oligodendrocytes through life and play crucial roles in brain homeostasis and plasticity during health and disease. Cannabinoid compounds acting through CB
1 receptors promote the proliferation and differentiation of OPCs in vitro and facilitate developmental myelination and myelin repair in vivo . However, CB1 receptor expression in adult OPCs in situ has not been corroborated by anatomical studies and the contribution of this receptor population to the (re)myelination effects of cannabinoids remains a matter of debate. Using electron microscopy methods applied to NG2-EYFP reporter mice we assessed the localization of CB1 receptors in OPCs of the adult mouse hippocampus. To control for the specificity of CB1 receptor immunostaining we generated transgenic mice bearing EYFP expression in NG2 glia and wild-type (NG2-EYFP-CB1 +/+ ) and knockout (NG2-EYFP-CB1 -/- ) for CB1 receptors. Double immunogold and immunoperoxidase labeling for CB1 and EYFP, respectively, revealed that CB1 receptors are present in a low proportion of NG2 positive profiles within hippocampal s tratum radiatum of NG2-EYFP-CB1 +/+ mice. Quantitative analysis of immunogold particles in synaptic structures and NG2 profiles showed that CB1 receptors are expressed at lower density in adult OPCs than in glutamatergic cells of the rodent hippocampus. These results highlight the presence of CB1 receptors in adult OPCs thus providing an anatomical substrate for the remyelination promoting effects of cannabinoids and open a novel perspective on the roles of the endocannabinoid system in brain physiology through the modulation of NG2 glia., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Manterola, Chara, Aguado, Palazuelos, Matute and Mato.)- Published
- 2022
- Full Text
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28. Cannabinoid CB 1 receptor gene inactivation in oligodendrocyte precursors disrupts oligodendrogenesis and myelination in mice.
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Sánchez-de la Torre A, Aguado T, Huerga-Gómez A, Santamaría S, Gentile A, Chara JC, Matute C, Monory K, Mato S, Guzmán M, Lutz B, Galve-Roperh I, and Palazuelos J
- Subjects
- Animals, Cell Differentiation physiology, Gene Silencing, Mice, Myelin Sheath metabolism, Oligodendroglia metabolism, Cannabinoids pharmacology, Oligodendrocyte Precursor Cells metabolism, Receptor, Cannabinoid, CB1 metabolism
- Abstract
Cannabinoids are known to modulate oligodendrogenesis and developmental CNS myelination. However, the cell-autonomous action of these compounds on oligodendroglial cells in vivo, and the molecular mechanisms underlying these effects have not yet been studied. Here, by using oligodendroglial precursor cell (OPC)-targeted genetic mouse models, we show that cannabinoid CB
1 receptors exert an essential role in modulating OPC differentiation at the critical periods of postnatal myelination. We found that selective genetic inactivation of CB1 receptors in OPCs in vivo perturbs oligodendrogenesis and postnatal myelination by altering the RhoA/ROCK signaling pathway, leading to hypomyelination, and motor and cognitive alterations in young adult mice. Conversely, pharmacological CB1 receptor activation, by inducing E3 ubiquitin ligase-dependent RhoA proteasomal degradation, promotes oligodendrocyte development and CNS myelination in OPCs, an effect that was not evident in OPC-specific CB1 receptor-deficient mice. Moreover, pharmacological inactivation of ROCK in vivo overcomes the defects in oligodendrogenesis and CNS myelination, and behavioral alterations found in OPC-specific CB1 receptor-deficient mice. Overall, this study supports a cell-autonomous role for CB1 receptors in modulating oligodendrogenesis in vivo, which may have a profound impact on the scientific knowledge and therapeutic manipulation of CNS myelination by cannabinoids., (© 2022. The Author(s).)- Published
- 2022
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29. Δ 9 -Tetrahydrocannabinol promotes functional remyelination in the mouse brain.
- Author
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Aguado T, Huerga-Gómez A, Sánchez-de la Torre A, Resel E, Chara JC, Matute C, Mato S, Galve-Roperh I, Guzman M, and Palazuelos J
- Subjects
- Animals, Cell Differentiation, Dronabinol pharmacology, Mice, Oligodendroglia, Demyelinating Diseases chemically induced, Demyelinating Diseases drug therapy, Remyelination, White Matter
- Abstract
Background and Purpose: Research on demyelinating disorders aims to find novel molecules that are able to induce oligodendrocyte precursor cell differentiation to promote central nervous system remyelination and functional recovery. Δ
9 -Tetrahydrocannabinol (THC), the most prominent active constituent of the hemp plant Cannabis sativa, confers neuroprotection in animal models of demyelination. However, the possible effect of THC on myelin repair has never been studied., Experimental Approach: By using oligodendroglia-specific reporter mouse lines in combination with two models of toxin-induced demyelination, we analysed the effect of THC on the processes of oligodendrocyte regeneration and functional remyelination., Key Results: We show that THC administration enhanced oligodendrocyte regeneration, white matter remyelination and motor function recovery. THC also promoted axonal remyelination in organotypic cerebellar cultures. THC remyelinating action relied on the induction of oligodendrocyte precursor differentiation upon cell cycle exit and via CB1 cannabinoid receptor activation., Conclusions and Implications: Overall, our study identifies THC administration as a promising pharmacological strategy aimed to promote functional CNS remyelination in demyelinating disorders., (© 2021 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)- Published
- 2021
- Full Text
- View/download PDF
30. The need for a global COVID-19 maternal immunisation research plan.
- Author
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Bardají A, Sevene E, Cutland C, Menéndez C, Omer SB, Aguado T, and Muñoz FM
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- Biomedical Research, COVID-19 Vaccines standards, Clinical Trials as Topic, Female, Humans, Internationality, Pregnancy, Pregnancy Complications, Infectious prevention & control, Research Design, SARS-CoV-2, COVID-19 prevention & control, COVID-19 Vaccines adverse effects, Immunization
- Published
- 2021
- Full Text
- View/download PDF
31. Δ 9 -Tetrahydrocannabinol promotes oligodendrocyte development and CNS myelination in vivo.
- Author
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Huerga-Gómez A, Aguado T, Sánchez-de la Torre A, Bernal-Chico A, Matute C, Mato S, Guzmán M, Galve-Roperh I, and Palazuelos J
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- Animals, Mechanistic Target of Rapamycin Complex 1, Mice, Oligodendroglia, Receptors, Cannabinoid, Dronabinol pharmacology, Endocannabinoids
- Abstract
Δ
9 -Tetrahydrocannabinol (THC), the main bioactive compound found in the plant Cannabis sativa, exerts its effects by activating cannabinoid receptors present in many neural cells. Cannabinoid receptors are also physiologically engaged by endogenous cannabinoid compounds, the so-called endocannabinoids. Specifically, the endocannabinoid 2-arachidonoylglycerol has been highlighted as an important modulator of oligodendrocyte (OL) development at embryonic stages and in animal models of demyelination. However, the potential impact of THC exposure on OL lineage progression during the critical periods of postnatal myelination has never been explored. Here, we show that acute THC administration at early postnatal ages in mice enhanced OL development and CNS myelination in the subcortical white matter by promoting oligodendrocyte precursor cell cycle exit and differentiation. Mechanistically, THC-induced-myelination was mediated by CB1 and CB2 cannabinoid receptors, as demonstrated by the blockade of THC actions by selective receptor antagonists. Moreover, the THC-mediated modulation of oligodendroglial differentiation relied on the activation of the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway, as mTORC1 pharmacological inhibition prevented the THC effects. Our study identifies THC as an effective pharmacological strategy to enhance oligodendrogenesis and CNS myelination in vivo., (© 2020 The Authors. GLIA published by Wiley Periodicals LLC.)- Published
- 2021
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32. Raloxifene and n-Acetylcysteine Ameliorate TGF-Signalling in Fibroblasts from Patients with Recessive Dominant Epidermolysis Bullosa.
- Author
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Aguado T, García M, García A, Ferrer-Mayorga G, Martínez-Santamaría L, Del Río M, Botella LM, and Sánchez-Puelles JM
- Subjects
- Activin Receptors, Type II genetics, Activin Receptors, Type II metabolism, Antioxidants pharmacology, Case-Control Studies, Collagen Type VII genetics, Collagen Type VII metabolism, Endoglin genetics, Endoglin metabolism, Epidermolysis Bullosa metabolism, Epidermolysis Bullosa pathology, Estrogen Antagonists pharmacology, Extracellular Matrix Proteins genetics, Extracellular Matrix Proteins metabolism, Fibroblasts metabolism, Fibroblasts pathology, Fibrosis, Gene Expression Regulation, Humans, Inheritance Patterns, Primary Cell Culture, Receptor, Transforming Growth Factor-beta Type I genetics, Receptor, Transforming Growth Factor-beta Type I metabolism, Severity of Illness Index, Signal Transduction, Skin drug effects, Skin metabolism, Skin pathology, Smad Proteins genetics, Smad Proteins metabolism, Transforming Growth Factor beta1 metabolism, Acetylcysteine pharmacology, Drug Repositioning, Epidermolysis Bullosa genetics, Fibroblasts drug effects, Raloxifene Hydrochloride pharmacology, Transforming Growth Factor beta1 genetics
- Abstract
Recessive dystrophic epidermolysis bullosa (RDEB) is a severe skin disease caused by mutation of the COL7A1 gene. RDEB is associated with high levels of TGF-β1, which is likely to be involved in the fibrosis that develops in this disease. Endoglin (CD105) is a type III coreceptor for TGF-β1 and its overexpression in fibroblasts deregulates physiological Smad/Alk1/Alk5 signalling, repressing the synthesis of TGF-β1 and extracellular matrix (ECM) proteins. Raloxifene is a specific estrogen receptor modulator designated as an orphan drug for hereditary hemorrhagic telangiectasia, a rare vascular disease. Raloxifene stimulates endoglin synthesis, which could attenuate fibrosis. By contrast, the antioxidant N-acetylcysteine may have therapeutic value to rectify inflammation, fibrosis and endothelial dysfunction. Thus, we present here a repurposing strategy based on the molecular and functional screening of fibroblasts from RDEB patients with these drugs, leading us to propose the repositioning of these two well-known drugs currently in clinical use, raloxifene and N-acetylcysteine, to counteract fibrosis and inflammation in RDEB. Both compounds modulate the profibrotic events that may ultimately be responsible for the clinical manifestations in RDEB, suggesting that these findings may also be relevant for other diseases in which fibrosis is an important pathophysiological event.
- Published
- 2020
- Full Text
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33. Targeting β2-Adrenergic Receptors Shows Therapeutical Benefits in Clear Cell Renal Cell Carcinoma from Von Hippel-Lindau Disease.
- Author
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Albiñana V, Gallardo-Vara E, de Rojas-P I, Recio-Poveda L, Aguado T, Canto-Cano A, Aguirre DT, Serra MM, González-Peramato P, Martínez-Piñeiro L, Cuesta AM, and Botella LM
- Abstract
Von Hippel-Lindau (VHL), is a rare autosomal dominant inherited cancer in which the lack of VHL protein triggers the development of multisystemic tumors such us retinal hemangioblastomas (HB), CNS-HB, and clear cell renal cell carcinoma (ccRCC). ccRCC ranks third in terms of incidence and first in cause of death. Standard systemic therapies for VHL-ccRCC have shown limited response, with recurrent surgeries being the only effective treatment. Targeting of β2-adrenergic receptor (ADRB) has shown therapeutic antitumor benefits on VHL-retinal HB (clinical trial) and VHL-CNS HB (in vitro). Therefore, the in vitro and in vivo antitumor benefits of propranolol (ADRB-1,2 antagonist) and ICI-118,551 (ADRB-2 antagonist) on VHL
-/- ccRCC primary cultures and 786-O tumor cell lines have been addressed. Propranolol and ICI-118,551 activated apoptosis inhibited gene and protein expression of HIF-2α, CAIX, and VEGF, and impaired partially the nuclear internalization of HIF-2α and NFĸB/p65. Moreover, propranolol and ICI-118,551 reduced tumor growth on two in vivo xenografts. Finally, ccRCC patients receiving propranolol as off-label treatment have shown a positive therapeutic response for two years on average. In summary, propranolol and ICI-118,551 have shown antitumor benefits in VHL-derived ccRCC, and since ccRCCs comprise 63% of the total RCCs, targeting ADRB2 becomes a promising drug for VHL and other non-VHL tumors.- Published
- 2020
- Full Text
- View/download PDF
34. The life-course approach to vaccination: Harnessing the benefits of vaccination throughout life.
- Author
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Tate J, Aguado T, Belie J, Holt D, Karafillakis E, Larson HJ, Nye S, Salisbury D, Votta M, and Wait S
- Subjects
- Age Factors, Health Impact Assessment, Humans, Immunization Programs methods, Immunization Schedule, Public Health, Vaccine-Preventable Diseases epidemiology, Vaccine-Preventable Diseases prevention & control, Vaccination methods, Vaccines immunology
- Abstract
Vaccination beyond childhood brings significant benefits at the individual, community and socio-economic levels. Despite this, immunisation programmes often fail to deliver the vaccines which could protect those at risk of vaccine-preventable diseases. In this commentary, we argue that the benefits of vaccination beyond childhood must be more widely understood and furthermore, that action must be taken by policymakers, healthcare professionals and patient and civil society organisations to ensure that the benefits of vaccination are fully realised. We outline five areas where change is needed to ensure vaccination across the life-course becomes truly embedded in national immunisation programmes. This includes investing in robust data collection and analysis; ensuring coordinated, multidisciplinary leadership from the top; engaging healthcare professionals; changing public perceptions of vaccination; and integrating vaccination into schools and workplaces., (Copyright © 2019 Elsevier Ltd. All rights reserved.)
- Published
- 2019
- Full Text
- View/download PDF
35. 11PS04 is a new chemical entity identified by microRNA-based biosensing with promising therapeutic potential against cancer stem cells.
- Author
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Aguado T, Romero-Revilla JA, Granados R, Campuzano S, Torrente-Rodríguez RM, Cuesta ÁM, Albiñana V, Botella LM, Santamaría S, Garcia-Sanz JA, Pingarrón JM, Sánchez-Sancho F, and Sánchez-Puelles JM
- Subjects
- Animals, Antineoplastic Agents pharmacology, Carcinogenesis drug effects, Carcinogenesis pathology, Cell Line, Tumor, Cell Proliferation drug effects, Cell Survival drug effects, Female, Gene Expression Regulation, Neoplastic drug effects, Glioma pathology, Magnetic Phenomena, Mammary Glands, Animal drug effects, Mammary Glands, Animal pathology, Mice, Neoplastic Stem Cells drug effects, Neoplastic Stem Cells metabolism, Oxazoles chemistry, Reproducibility of Results, Spheroids, Cellular drug effects, Spheroids, Cellular metabolism, Spheroids, Cellular pathology, Temozolomide pharmacology, Xenograft Model Antitumor Assays, Biosensing Techniques, MicroRNAs metabolism, Neoplastic Stem Cells pathology, Oxazoles pharmacology
- Abstract
Phenotypic drug discovery must take advantage of the large amount of clinical data currently available. In this sense, the impact of microRNAs (miRs) on human disease and clinical therapeutic responses is becoming increasingly well documented. Accordingly, it might be possible to use miR-based signatures as phenotypic read-outs of pathological status, for example in cancer. Here, we propose to use the information accumulating regarding the biology of miRs from clinical research in the preclinical arena, adapting it to the use of miR biosensors in the earliest steps of drug screening. Thus, we have used an amperometric dual magnetosensor capable of monitoring a miR-21/miR-205 signature to screen for new drugs that restore these miRs to non-tumorigenic levels in cell models of breast cancer and glioblastoma. In this way we have been able to identify a new chemical entity, 11PS04 ((3aR,7aS)-2-(3-propoxyphenyl)-7,7a-dihydro-3aH-pyrano[3,4-d]oxazol-6(4H)-one), the therapeutic potential of which was suggested in mechanistic assays of disease models, including 3D cell culture (oncospheres) and xenografts. These assays highlighted the potential of this compound to attack cancer stem cells, reducing the growth of breast and glioblastoma tumors in vivo. These data demonstrate the enhanced chain of translatability of this strategy, opening up new perspectives for drug-discovery pipelines and highlighting the potential of miR-based electro-analytical sensors as efficient tools in modern drug discovery.
- Published
- 2019
- Full Text
- View/download PDF
36. Multifunctional Albumin-Stabilized Gold Nanoclusters for the Reduction of Cancer Stem Cells.
- Author
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Latorre A, Latorre A, Castellanos M, Rodriguez Diaz C, Lazaro-Carrillo A, Aguado T, Lecea M, Romero-Pérez S, Calero M, Sanchez-Puelles JM, Villanueva Á, and Somoza Á
- Abstract
Controlled delivery of multiple chemotherapeutics can improve the effectiveness of treatments and reduce side effects and relapses. Here in, we used albumin-stabilized gold nanoclusters modified with doxorubicin and SN38 (AuNCs-DS) as combined therapy for cancer. The chemotherapeutics are conjugated to the nanostructures using linkers that release them when exposed to different internal stimuli (Glutathione and pH). This system has shown potent antitumor activity against breast and pancreatic cancer cells. Our studies indicate that the antineoplastic activity observed may be related to the reinforced DNA damage generated by the combination of the drugs. Moreover, this system presented antineoplastic activity against mammospheres, a culturing model for cancer stem cells, leading to an efficient reduction of the number of oncospheres and their size. In summary, the nanostructures reported here are promising carriers for combination therapy against cancer and particularly to cancer stem cells.
- Published
- 2019
- Full Text
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37. Maternal immunization: A call to accelerate progress.
- Author
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Bardají A, MacDonald NE, Omer SB, and Aguado T
- Subjects
- Female, Humans, Infant, Infant Mortality, Infant, Newborn, Respiratory Syncytial Viruses pathogenicity, Streptococcus pathogenicity, Immunization methods, Respiratory Syncytial Viruses immunology, Streptococcus immunology
- Abstract
Maternal immunization provides an excellent evidence-based strategy for preventing severe disease and decreasing neonatal and infant mortality. A substantial proportion of these deaths are due to infectious diseases, most of them vaccine-preventable, then, there is a real opportunity for intervention. Maternal immunization has been an underexploited area for many years, with the exception of neonatal tetanus. There are now programs for influenza and acellular pertussis vaccination in many countries and two maternal vaccine targets under development are focused on decreasing the burden of infant respiratory syncytial virus (RSV) and Group B Streptococcus (GBS). Bodies like the Strategic Advisory Group of Experts (SAGE) on Immunization established by the WHO, the Global Vaccine Action Plan (GVAP) and Gavi, The Vaccine Alliance, have recognized the relevance of maternal immunization on several occasions. However, why is the field not moving faster, as one might expect? Major initiatives and programs should consider spelling out more clearly the role and benefits of this intervention and calling for specific actions, including future strategic approaches for the post 2020 immunization strategy following the GVAP; and single out the area as one of its priorities as a key component of immunization across the life course. While waiting for the new vaccines like RSV and GBS and optimizing the use of influenza and pertussis there is momentum now to coordinate efforts, address the missing information and action gaps, and call to accelerate progress., (Copyright © 2019 Elsevier Ltd. All rights reserved.)
- Published
- 2019
- Full Text
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38. Telomere Length Defines the Cardiomyocyte Differentiation Potency of Mouse Induced Pluripotent Stem Cells.
- Author
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Aguado T, Gutiérrez FJ, Aix E, Schneider RP, Giovinazzo G, Blasco MA, and Flores I
- Subjects
- Animals, Ascorbic Acid pharmacology, Cell Lineage drug effects, Cell Proliferation drug effects, Cell Size drug effects, Collagen metabolism, Embryoid Bodies cytology, Embryoid Bodies metabolism, Mice, Myocytes, Cardiac drug effects, Cell Differentiation drug effects, Induced Pluripotent Stem Cells cytology, Induced Pluripotent Stem Cells metabolism, Myocytes, Cardiac cytology, Myocytes, Cardiac metabolism, Telomere Homeostasis drug effects
- Abstract
Induced pluripotent stem cells (iPSCs) can be differentiated in vitro and in vivo to all cardiovascular lineages and are therefore a promising cell source for cardiac regenerative therapy. However, iPSC lines do not all differentiate into cardiomyocytes (CMs) with the same efficiency. Here, we show that telomerase-competent iPSCs with relatively long telomeres and high expression of the shelterin-complex protein TRF1 (iPSC
highT ) differentiate sooner and more efficiently into CMs than those with relatively short telomeres and low TRF1 expression (iPSClowT ). Ascorbic acid, an enhancer of cardiomyocyte differentiation, further increases the cardiomyocyte yield from iPSChighT but does not rescue the cardiomyogenic potential of iPSClowT . Interestingly, although iPSCslowT differentiate very poorly to the mesoderm and endoderm lineages, they differentiate very efficiently to the ectoderm lineage, indicating that cell fate can be determined by in vitro selection of iPSCs with different telomere content. Our findings highlight the importance of selecting iPSCs with ample telomere reserves in order to generate high numbers of CMs in a fast, reliable, and efficient way. Stem Cells 2017;35:362-373., (© 2016 AlphaMed Press.)- Published
- 2017
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39. Postnatal telomere dysfunction induces cardiomyocyte cell-cycle arrest through p21 activation.
- Author
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Aix E, Gutiérrez-Gutiérrez Ó, Sánchez-Ferrer C, Aguado T, and Flores I
- Subjects
- Anaphase, Animals, Animals, Newborn, Cell Proliferation, DNA Damage, DNA Repair, Mice, Inbred C57BL, Models, Biological, Telomerase metabolism, Telomere Homeostasis, Cell Cycle Checkpoints, Cyclin-Dependent Kinase Inhibitor p21 metabolism, Myocytes, Cardiac cytology, Myocytes, Cardiac metabolism, Telomere metabolism
- Abstract
The molecular mechanisms that drive mammalian cardiomyocytes out of the cell cycle soon after birth remain largely unknown. Here, we identify telomere dysfunction as a critical physiological signal for cardiomyocyte cell-cycle arrest. We show that telomerase activity and cardiomyocyte telomere length decrease sharply in wild-type mouse hearts after birth, resulting in cardiomyocytes with dysfunctional telomeres and anaphase bridges and positive for the cell-cycle arrest protein p21. We further show that premature telomere dysfunction pushes cardiomyocytes out of the cell cycle. Cardiomyocytes from telomerase-deficient mice with dysfunctional telomeres (G3 Terc(-/-)) show precocious development of anaphase-bridge formation, p21 up-regulation, and binucleation. In line with these findings, the cardiomyocyte proliferative response after cardiac injury was lost in G3 Terc(-/-) newborns but rescued in G3 Terc(-/-)/p21(-/-) mice. These results reveal telomere dysfunction as a crucial signal for cardiomyocyte cell-cycle arrest after birth and suggest interventions to augment the regeneration capacity of mammalian hearts., (© 2016 Aix et al.)
- Published
- 2016
- Full Text
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40. The burden of vaccine-preventable diseases in pregnancy in low-resource settings.
- Author
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Bardají A, Steinhoff M, Macete E, Aguado T, and Menéndez C
- Subjects
- Cost of Illness, Developing Countries, Female, Humans, Pregnancy, Maternal Health Services organization & administration, Pregnancy Complications, Infectious prevention & control, Vaccination
- Published
- 2016
- Full Text
- View/download PDF
41. Telomerase Is Essential for Zebrafish Heart Regeneration.
- Author
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Bednarek D, González-Rosa JM, Guzmán-Martínez G, Gutiérrez-Gutiérrez Ó, Aguado T, Sánchez-Ferrer C, Marques IJ, Galardi-Castilla M, de Diego I, Gómez MJ, Cortés A, Zapata A, Jiménez-Borreguero LJ, Mercader N, and Flores I
- Subjects
- Animals, Cell Proliferation, Gene Expression, Gene Knockout Techniques, Myocardium enzymology, Myocytes, Cardiac physiology, Tissue Culture Techniques, Zebrafish, Heart physiology, Regeneration, Telomerase physiology, Zebrafish Proteins physiology
- Abstract
After myocardial infarction in humans, lost cardiomyocytes are replaced by an irreversible fibrotic scar. In contrast, zebrafish hearts efficiently regenerate after injury. Complete regeneration of the zebrafish heart is driven by the strong proliferation response of its cardiomyocytes to injury. Here we show that, after cardiac injury in zebrafish, telomerase becomes hyperactivated, and telomeres elongate transiently, preceding a peak of cardiomyocyte proliferation and full organ recovery. Using a telomerase-mutant zebrafish model, we found that telomerase loss drastically decreases cardiomyocyte proliferation and fibrotic tissue regression after cryoinjury and that cardiac function does not recover. The impaired cardiomyocyte proliferation response is accompanied by the absence of cardiomyocytes with long telomeres and an increased proportion of cardiomyocytes showing DNA damage and senescence characteristics. These findings demonstrate the importance of telomerase function in heart regeneration and highlight the potential of telomerase therapy as a means of stimulating cell proliferation upon myocardial infarction., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2015
- Full Text
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42. CB1 Cannabinoid Receptor-Dependent Activation of mTORC1/Pax6 Signaling Drives Tbr2 Expression and Basal Progenitor Expansion in the Developing Mouse Cortex.
- Author
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Díaz-Alonso J, Aguado T, de Salas-Quiroga A, Ortega Z, Guzmán M, and Galve-Roperh I
- Subjects
- Animals, Animals, Newborn, Cell Culture Techniques, Embryo, Mammalian, Eye Proteins genetics, Eye Proteins metabolism, Homeodomain Proteins genetics, Homeodomain Proteins metabolism, Ki-67 Antigen metabolism, Mechanistic Target of Rapamycin Complex 1, Mice, Mice, Transgenic, Multiprotein Complexes genetics, Multiprotein Complexes metabolism, Mutation genetics, Nerve Tissue Proteins metabolism, Organ Culture Techniques, PAX6 Transcription Factor, Paired Box Transcription Factors genetics, Paired Box Transcription Factors metabolism, RNA, Small Interfering genetics, RNA, Small Interfering metabolism, Receptor, Cannabinoid, CB1 genetics, Repressor Proteins genetics, Repressor Proteins metabolism, T-Box Domain Proteins genetics, TOR Serine-Threonine Kinases genetics, TOR Serine-Threonine Kinases metabolism, Cerebral Cortex cytology, Cerebral Cortex embryology, Cerebral Cortex growth & development, Gene Expression Regulation, Developmental genetics, Receptor, Cannabinoid, CB1 metabolism, Signal Transduction genetics, Stem Cells physiology, T-Box Domain Proteins metabolism
- Abstract
The CB1 cannabinoid receptor regulates cortical progenitor proliferation during embryonic development, but the molecular mechanism of this action remains unknown. Here, we report that CB1-deficient mouse embryos show premature cell cycle exit, decreased Pax6- and Tbr2-positive cell number, and reduced mammalian target of rapamycin complex 1 (mTORC1) activation in the ventricular and subventricular cortical zones. Pharmacological stimulation of the CB1 receptor in cortical slices and progenitor cell cultures activated the mTORC1 pathway and increased the number of Pax6- and Tbr2-expressing cells. Likewise, acute CB1 knockdown in utero reduced mTORC1 activation and cannabinoid-induced Tbr2-positive cell generation. Luciferase reporter and chromatin immunoprecipitation assays revealed that the CB1 receptor drives Tbr2 expression downstream of Pax6 induction in an mTORC1-dependent manner. Altogether, our results demonstrate that the CB1 receptor tunes dorsal telencephalic progenitor proliferation by sustaining the transcriptional activity of the Pax6-Tbr2 axis via the mTORC1 pathway, and suggest that alterations of CB1 receptor signaling, by producing the missexpression of progenitor identity determinants may contribute to neurodevelopmental alterations., (© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)
- Published
- 2015
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43. Effectively introducing a new meningococcal A conjugate vaccine in Africa: the Burkina Faso experience.
- Author
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Djingarey MH, Barry R, Bonkoungou M, Tiendrebeogo S, Sebgo R, Kandolo D, Lingani C, Preziosi MP, Zuber PL, Perea W, Hugonnet S, Dellepiane de Rey Tolve N, Tevi-Benissan C, Clark TA, Mayer LW, Novak R, Messonier NE, Berlier M, Toboe D, Nshimirimana D, Mihigo R, Aguado T, Diomandé F, Kristiansen PA, Caugant DA, and Laforce FM
- Subjects
- Burkina Faso epidemiology, Humans, Meningococcal Infections epidemiology, Vaccination methods, Immunization Programs organization & administration, Meningococcal Infections microbiology, Meningococcal Infections prevention & control, Meningococcal Vaccines administration & dosage, Meningococcal Vaccines immunology, Neisseria meningitidis, Serogroup A immunology
- Abstract
A new Group A meningococcal (Men A) conjugate vaccine, MenAfriVac™, was prequalified by the World Health Organization (WHO) in June 2010. Because Burkina Faso has repeatedly suffered meningitis epidemics due to Group A Neisseria meningitidis special efforts were made to conduct a country-wide campaign with the new vaccine in late 2010 and before the onset of the next epidemic meningococcal disease season beginning in January 2011. In the ensuing five months (July-November 2010) the following challenges were successfully managed: (1) doing a large safety study and registering the new vaccine in Burkina Faso; (2) developing a comprehensive communication plan; (3) strengthening the surveillance system with particular attention to improving the capacity for real-time polymerase chain reaction (PCR) testing of spinal fluid specimens; (4) improving cold chain capacity and waste disposal; (5) developing and funding a sound campaign strategy; and (6) ensuring effective collaboration across all partners. Each of these issues required specific strategies that were managed through a WHO-led consortium that included all major partners (Ministry of Health/Burkina Faso, Serum Institute of India Ltd., UNICEF, Global Alliance for Vaccines and Immunization, Meningitis Vaccine Project, CDC/Atlanta, and the Norwegian Institute of Public Health/Oslo). Biweekly teleconferences that were led by WHO ensured that problems were identified in a timely fashion. The new meningococcal A conjugate vaccine was introduced on December 6, 2010, in a national ceremony led by His Excellency Blaise Compaore, the President of Burkina Faso. The ensuing 10-day national campaign was hugely successful, and over 11.4 million Burkinabes between the ages of 1 and 29 years (100% of target population) were vaccinated. African national immunization programs are capable of achieving very high coverage for a vaccine desired by the public, introduced in a well-organized campaign, and supported at the highest political level. The Burkina Faso success augurs well for further rollout of the Men A conjugate vaccine in meningitis belt countries., (Copyright © 2012 Elsevier Ltd. All rights reserved.)
- Published
- 2012
- Full Text
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44. Evaluation of a rapid dipstick (Crystal VC) for the diagnosis of cholera in Zanzibar and a comparison with previous studies.
- Author
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Ley B, Khatib AM, Thriemer K, von Seidlein L, Deen J, Mukhopadyay A, Chang NY, Hashim R, Schmied W, Busch CJ, Reyburn R, Wierzba T, Clemens JD, Wilfing H, Enwere G, Aguado T, Jiddawi MS, Sack D, and Ali SM
- Subjects
- Humans, Reproducibility of Results, Sensitivity and Specificity, Tanzania, Cholera diagnosis, Reagent Kits, Diagnostic
- Abstract
Background: The gold standard for the diagnosis of cholera is stool culture, but this requires laboratory facilities and takes at least 24 hours. A rapid diagnostic test (RDT) that can be used by minimally trained staff at treatment centers could potentially improve the reporting and management of cholera outbreaks., Methods: We evaluated the Crystal VC™ RDT under field conditions in Zanzibar in 2009. Patients presenting to treatment centers with watery diarrhea provided a stool sample for rapid diagnostic testing. Results were compared to stool culture performed in a reference laboratory. We assessed the overall performance of the RDT and evaluated whether previous intake of antibiotics, intravenous fluids, location of testing, and skill level of the technician affected the RDT results., Results: We included stool samples from 624 patients. Compared to culture, the overall sensitivity of the RDT was 93.1% (95%CI: 88.7 to 96.2%), specificity was 49.2% (95%CI: 44.3 to 54.1%), the positive predictive value was 47.0% (95%CI: 42.1 to 52.0%) and the negative predictive value was 93.6% (95%CI: 89.6 to 96.5%). The overall false positivity rate was 50.8% (213/419); fieldworkers frequently misread very faint test lines as positive., Conclusion: The observed sensitivity of the Crystal VC RDT evaluated was similar compared to earlier versions, while specificity was poorer. The current version of the RDT could potentially be used as a screening tool in the field. Because of the high proportion of false positive results when field workers test stool specimens, positive results will need to be confirmed with stool culture.
- Published
- 2012
- Full Text
- View/download PDF
45. Rotavirus vaccines for infants in developing countries in Africa and Asia: considerations from a world health organization-sponsored consultation.
- Author
-
Steele AD, Patel M, Parashar UD, Victor JC, Aguado T, and Neuzil KM
- Subjects
- Africa, Asia, Clinical Trials as Topic, Cost-Benefit Analysis, Humans, Immunization Programs, Infant, Infant, Newborn, Referral and Consultation, Rotavirus Vaccines adverse effects, Rotavirus Vaccines economics, Rotavirus Vaccines immunology, Vaccination, World Health Organization
- Abstract
The World Health Organization (WHO) and its international partners have prioritized the development of rotavirus vaccines for the past 3 decades. In November 2005, the WHO's Strategic Advisory Group of Experts first reviewed the clinical efficacy data from 2 new live attenuated oral rotavirus vaccines, which demonstrated excellent protective efficacy against severe rotavirus disease in regions where they were evaluated. Despite these successes, the WHO has urged the clinical evaluation of these vaccines in populations of Africa and Asia, where most of the deaths due to rotavirus occur, and has emphasized the need for ongoing postlicensure safety monitoring in countries introducing vaccines. Clinical studies in Africa and Asia will soon provide data on the efficacy of both new vaccines in these populations. A WHO international consultative meeting convened to evaluate how to use these imminent data for the future use of rotavirus vaccines in developing countries. In brief, it was agreed that (1) even vaccines with lesser efficacy in developing countries, compared with industrialized countries, would still lead to substantial public health benefits and would be cost-effective in saving lives in Africa and Asia; (2) criteria, such as the WHO mortality strata and local epidemiology of rotavirus infection, would be appropriate measures for extrapolating the clinical data to other regions and countries; and (3) research toward understanding the programmatic limitations of rotavirus vaccine use may help develop strategies to improve vaccine uptake and overall impact.
- Published
- 2009
- Full Text
- View/download PDF
46. Microglial CB2 cannabinoid receptors are neuroprotective in Huntington's disease excitotoxicity.
- Author
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Palazuelos J, Aguado T, Pazos MR, Julien B, Carrasco C, Resel E, Sagredo O, Benito C, Romero J, Azcoitia I, Fernández-Ruiz J, Guzmán M, and Galve-Roperh I
- Subjects
- Animals, Anti-Bacterial Agents pharmacology, Biomarkers metabolism, Corpus Striatum cytology, Corpus Striatum drug effects, Corpus Striatum metabolism, Corpus Striatum pathology, Humans, Huntingtin Protein, Magnetic Resonance Imaging, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Minocycline pharmacology, Nerve Degeneration metabolism, Nerve Tissue Proteins genetics, Nerve Tissue Proteins metabolism, Nuclear Proteins genetics, Nuclear Proteins metabolism, Quinolinic Acid pharmacology, Receptor, Cannabinoid, CB2 genetics, Rotarod Performance Test, Seizures physiopathology, Huntington Disease metabolism, Huntington Disease pathology, Huntington Disease physiopathology, Microglia metabolism, Neuroprotective Agents metabolism, Receptor, Cannabinoid, CB2 metabolism
- Abstract
Cannabinoid-derived drugs are promising agents for the development of novel neuroprotective strategies. Activation of neuronal CB(1) cannabinoid receptors attenuates excitotoxic glutamatergic neurotransmission, triggers prosurvival signalling pathways and palliates motor symptoms in animal models of neurodegenerative disorders. However, in Huntington's disease there is a very early downregulation of CB(1) receptors in striatal neurons that, together with the undesirable psychoactive effects triggered by CB(1) receptor activation, foster the search for alternative pharmacological treatments. Here, we show that CB(2) cannabinoid receptor expression increases in striatal microglia of Huntington's disease transgenic mouse models and patients. Genetic ablation of CB(2) receptors in R6/2 mice, that express human mutant huntingtin exon 1, enhanced microglial activation, aggravated disease symptomatology and reduced mice lifespan. Likewise, induction of striatal excitotoxicity in CB(2) receptor-deficient mice by quinolinic acid administration exacerbated brain oedema, microglial activation, proinflammatory-mediator state and medium-sized spiny neuron degeneration. Moreover, administration of CB(2) receptor-selective agonists to wild-type mice subjected to excitotoxicity reduced neuroinflammation, brain oedema, striatal neuronal loss and motor symptoms. Studies on ganciclovir-induced depletion of astroglial proliferation in transgenic mice expressing thymidine kinase under the control of the glial fibrillary acidic protein promoter excluded the participation of proliferating astroglia in CB(2) receptor-mediated actions. These findings support a pivotal role for CB(2) receptors in attenuating microglial activation and preventing neurodegeneration that may pave the way to new therapeutic strategies for neuroprotection in Huntington's disease as well as in other neurodegenerative disorders with a significant excitotoxic component.
- Published
- 2009
- Full Text
- View/download PDF
47. The endocannabinoid system and the regulation of neural development: potential implications in psychiatric disorders.
- Author
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Galve-Roperh I, Palazuelos J, Aguado T, and Guzmán M
- Subjects
- Animals, Cell Proliferation, Cognition physiology, Humans, Receptors, Cannabinoid physiology, Signal Transduction physiology, Stem Cells physiology, Brain cytology, Brain growth & development, Brain physiopathology, Cannabinoid Receptor Modulators physiology, Endocannabinoids, Neurogenesis physiology, Psychotic Disorders metabolism, Psychotic Disorders physiopathology
- Abstract
During brain development, functional neurogenesis is achieved by the concerted action of various steps that include the expansion of progenitor cells, neuronal specification, and establishment of appropriate synapses. Brain patterning and regionalization is regulated by a variety of extracellular signals and morphogens that, together with neuronal activity, orchestrate and regulate progenitor proliferation, differentiation, and neuronal maturation. In the adult brain, CB(1) cannabinoid receptors are expressed at very high levels in selective areas and are engaged by endocannabinoids, which act as retrograde messengers controlling neuronal function and preventing excessive synaptic activity. In addition, the endocannabinoid system is present at early developmental stages of nervous system formation. Recent studies have provided novel information on the role of this endogenous neuromodulatory system in the control of neuronal specification and maturation. Thus, cannabinoid receptors and locally produced endocannabinoids regulate neural progenitor proliferation and pyramidal specification of projecting neurons. CB(1) receptors also control axonal navigation, migration, and positioning of interneurons and excitatory neurons. Loss of function studies by genetic ablation or pharmacological blockade of CB(1) receptors interferes with long-range subcortical projections and, likewise, prenatal cannabinoid exposure induces different functional alterations in the adult brain. Potential implications of these new findings, such as the participation of the endocannabinoid system in the pathogenesis of neurodevelopmental disorders (e.g., schizophrenia) and the regulation of neurogenesis in brain depression, are discussed herein.
- Published
- 2009
- Full Text
- View/download PDF
48. The CB(2) cannabinoid receptor controls myeloid progenitor trafficking: involvement in the pathogenesis of an animal model of multiple sclerosis.
- Author
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Palazuelos J, Davoust N, Julien B, Hatterer E, Aguado T, Mechoulam R, Benito C, Romero J, Silva A, Guzmán M, Nataf S, and Galve-Roperh I
- Subjects
- Animals, Bone Marrow Cells cytology, Bone Marrow Cells metabolism, Cells, Cultured, Disease Models, Animal, Gene Expression Regulation, Humans, Mice, Mice, Knockout, Multiple Sclerosis genetics, Receptor, Cannabinoid, CB2 deficiency, Receptor, Cannabinoid, CB2 genetics, Spinal Cord cytology, Spinal Cord metabolism, Cell Movement, Multiple Sclerosis metabolism, Multiple Sclerosis pathology, Myeloid Progenitor Cells cytology, Myeloid Progenitor Cells metabolism, Receptor, Cannabinoid, CB2 metabolism
- Abstract
Cannabinoids are potential agents for the development of therapeutic strategies against multiple sclerosis. Here we analyzed the role of the peripheral CB(2) cannabinoid receptor in the control of myeloid progenitor cell trafficking toward the inflamed spinal cord and their contribution to microglial activation in an animal model of multiple sclerosis (experimental autoimmune encephalomyelitis, EAE). CB(2) receptor knock-out mice showed an exacerbated clinical score of the disease when compared with their wild-type littermates, and this occurred in concert with extended axonal loss, T-lymphocyte (CD4(+)) infiltration, and microglial (CD11b(+)) activation. Immature bone marrow-derived CD34(+) myeloid progenitor cells, which play a role in neuroinflammatory pathologies, were shown to express CB(2) receptors and to be abundantly recruited toward the spinal cords of CB(2) knock-out EAE mice. Bone marrow-derived cell transfer experiments further evidenced the increased contribution of these cells to microglial replenishment in the spinal cords of CB(2)-deficient animals. In line with these observations, selective pharmacological CB(2) activation markedly reduced EAE symptoms, axonal loss, and microglial activation. CB(2) receptor manipulation altered the expression pattern of different chemokines (CCL2, CCL3, CCL5) and their receptors (CCR1, CCR2), thus providing a mechanistic explanation for its role in myeloid progenitor recruitment during neuroinflammation. These findings demonstrate the protective role of CB(2) receptors in EAE pathology; provide evidence for a new site of CB(2) receptor action, namely the targeting of myeloid progenitor trafficking and its contribution to microglial activation; and support the potential use of non-psychoactive CB(2) agonists in therapeutic strategies for multiple sclerosis and other neuroinflammatory disorders.
- Published
- 2008
- Full Text
- View/download PDF
49. Mechanisms of control of neuron survival by the endocannabinoid system.
- Author
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Galve-Roperh I, Aguado T, Palazuelos J, and Guzmán M
- Subjects
- Animals, Cell Survival physiology, Humans, Neurodegenerative Diseases physiopathology, Neuroglia metabolism, Receptor Protein-Tyrosine Kinases metabolism, Cannabinoid Receptor Modulators metabolism, Endocannabinoids, Neurons metabolism, Receptor, Cannabinoid, CB1 metabolism, Signal Transduction
- Abstract
Endocannabinoids act as retrograde messengers that, by inhibiting neurotransmitter release via presynaptic CB(1) cannabinoid receptors, regulate the functionality of many synapses. In addition, the endocannabinoid system participates in the control of neuron survival. Thus, CB(1) receptor activation has been shown to protect neurons from acute brain injury as well as in neuroinflammatory conditions and neurodegenerative diseases. Nonetheless, some studies have reported that cannabinoids can also exert neurotoxic actions. Cannabinoid neuroprotective activity relies on the inhibition of glutamatergic neurotransmission and on other various mechanisms, and is supported by the observation that the brain overproduces endocannabinoids upon damage. Coupling of neuronal CB(1) receptors to cell survival routes such as the phosphatidylinositol 3-kinase/Akt and extracellular signal-regulated kinase pathways may contribute to cannabinoid neuroprotective action. These pro-survival signals occur, at least in part, by the cross-talk between CB(1) receptors and growth factor tyrosine kinase receptors. Besides promoting neuroprotection, a role for the endocannabinoid system in the control of neurogenesis from neural progenitors has been put forward. In addition, activation of CB(2) cannabinoid receptors on glial cells may also participate in neuroprotection by limiting the extent of neuroinflammation. Altogether, these findings support that endocannabinoids constitute a new family of lipid mediators that act as instructive signals in the control of neuron survival.
- Published
- 2008
- Full Text
- View/download PDF
50. The CB1 cannabinoid receptor mediates excitotoxicity-induced neural progenitor proliferation and neurogenesis.
- Author
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Aguado T, Romero E, Monory K, Palazuelos J, Sendtner M, Marsicano G, Lutz B, Guzmán M, and Galve-Roperh I
- Subjects
- Animals, Hippocampus, Kainic Acid pharmacology, Mice, Mice, Knockout, Neurons drug effects, Receptor, Cannabinoid, CB1 deficiency, Stem Cells drug effects, Cell Proliferation drug effects, Fibroblast Growth Factor 2 metabolism, Nerve Regeneration drug effects, Neurons pathology, Neurotoxins pharmacology, Receptor, Cannabinoid, CB1 physiology, Stem Cells cytology
- Abstract
Endocannabinoids are lipid signaling mediators that exert an important neuromodulatory role and confer neuroprotection in several types of brain injury. Excitotoxicity and stroke can induce neural progenitor (NP) proliferation and differentiation as an attempt of neuroregeneration after damage. Here we investigated the mechanism of hippocampal progenitor cell engagement upon excitotoxicity induced by kainic acid administration and the putative involvement of the CB1 cannabinoid receptor in this process. Adult NPs express kainate receptors that mediate proliferation and neurosphere generation in vitro via CB1 cannabinoid receptors. Similarly, in vivo studies showed that excitotoxicity-induced hippocampal NPs proliferation and neurogenesis are abrogated in CB1-deficient mice and in wild-type mice administered with the selective CB1 antagonist rimonabant (N-piperidino-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-3-pyrazolecarboxamide; SR141716). Kainate stimulation increased basic fibroblast growth factor (bFGF) expression in cultured NPs in a CB1-dependent manner as this response was prevented by rimonabant and mimicked by endocannabinoids. Likewise, in vivo analyses showed that increased hippocampal expression of bFGF, as well as of brain-derived neurotrophic factor and epidermal growth factor, occurs upon excitotoxicity and that CB1 receptor ablation prevents this induction. Moreover, excitotoxicity increased the number of CB1+ bFGF+ cells, and this up-regulation preceded NP proliferation. In summary, our results show the involvement of the CB1 cannabinoid receptor in NP proliferation and neurogenesis induced by excitotoxic injury and support a role for bFGF signaling in this process.
- Published
- 2007
- Full Text
- View/download PDF
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