Ángel Pazos Carro (IP)

  • angel.pazos@unican.es
  • 942 201985
  • Neurobiological Basis of the Mechanism of Action of Drugs acting at the Central Nervous System
  • Principal Investigator
  • Neuropharmacology
  • Department of Cell & Molecular Signalling

​Professor Ángel Pazos is Principal Investigator of the "Neurobiological Bases of the Mechanism of Action of Drugs acting on the Central Nervous System" group of the Institute of Biomedicine and Biotechnology of Cantabria (University of Cantabria) and the group CB/07/09/0029 of the Biomedical Research Networking Centres of Mental Health (CIBERSAM). Prof. Pazos was awarded a Bachelor degree in Medicine from the University of Cantabria (1979) and a PhD degree in Medicine and Surgery (1982) from the same University. Later, he joined the group of Dr. José Palacios in SANDOZ (Basel, Switzerland), identifying and characterizing a wide variety of neurotransmitter receptor subtypes in both animal and human (postmortem) brain. There, he participated in the discovery and characterization of the first receptor subtypes for serotonin. Back in Spain (1985), he established as an independent researcher, focusing on the modulation of receptors in animal models of neuropsychiatric pathology, as well as in postmortem human brain samples. He did a sabbatical leave in Bethesda (NIH, NIMH, 1996) were he assayed new methodological approaches to analyze the brain signalling mechanisms in an integrative way, and with the aim of developing a stable program of collaboration with biotech and pharmaceutical companies. In the last years, he has focused in the study of major depression (both pathogenesis and drug development). He had supervised several PhD students, as well as transference work with several pharmaceutical and biotech companies. In the last years, he is devoted to institutional duties at the University, first as the former director of the Institute of Biomedicine and Biotechnology of Cantabria (2007-2012), then as Vicerrector de Investigación y Transferencia del Conocimiento (2012-2016), and since 2016 as Rector of the University of Cantabria.

Neurobiological Basis of the Mechanism of Action of Drugs acting at the Central Nervous System


Research lines 

The main research line of the group deals with the neurochemical and neuroplastic signals involved in the pathogeny of neuropsychiatric diseases (major depression, schizophrenia) and, associated to that,  in the mechanism of action of antidepressant and antipsychotic  drugs. The goals of our neuropharmacological research include the study of: 
    • The role of monoaminergic systems (manly serotonin, 5-HT) in these psychiatric diseases and their modulation by chronic administration of antidepressants, with special interest on 5-HT1 and 5-HT4 receptors
    • The identification of brain  neuroplastic and neurogenetic pathways that could be targets of new pharmacological strategies for the treatment of depression and schizophrenia (b-catenin, BDNF)
    • The relationship between central aminergic pathways and recently identified neuromodulator systems (endocannabinoid, mTOR) and its relevance n major depression

For this purpose, studies in laboratory animals, models of depression and psychosis, and in blood and postmortem samples from depressed and schizophrenic patients are carried out. Behavioural, pharmacological (in vivo assays, receptor labeling), cell biology (immunocytochemistry, neurogenesis), biochemical (second messengers, G proteins), electrophysiological (in vivo and slice recordings) and molecular approaches (gen silencing, transfected receptors) are used.

Other sublines of research of the group include: 
    • The neurobiological basis of the analgesic responses induced by antidepressants
    • The identification of the intracellular signaling mechanisms associated to 5-HT receptor subtypes
    • The analysis of polymorphisms for proteins of relevance for the etiopathogeny of depressive disorders 
    • The characterization of animal models of psychiatric disorders

Funding

    • CICYT, Ministerio de Ciencia e Innovación. Cannabidiol como acelerador de la respuesta farmacológica antidepresiva: una vía hacia la identificación de los mecanismos celulares implicados en la depresión (SAF2015-67457-R). Enero 2016-Diciembre 2018.
    • CICYT, Ministerio de Ciencia e Innovación. Fármacos antidepresivos y dianas de señalización intracelular: implicación de mecanismos de proliferación (SAF07-61862). Octubre 2007-Septiembre 2012
    • Neuroplasticity mechanisms involved in the fast antidepressant response of 5-HT4 receptor agonists: role of the Wnt-b-catenin and mTOR pathways (SAF2011-25020 ). Enero 2012-Diciembre 2014.
    • Instituto de Salud Carlos III. CIBER de Salud Mental, 2009-
    • Programa ZENIT,  Ministerio de Ciencia e Innovación (con BrainCo y FaesFarma SA).Nuevas aproximaciones en el tratamiento de las enfermedades del sistema nervioso. Enero 2010-Diciembre 2012


S 47445 counteracts the behavioral manifestations and hippocampal neuroplasticity changes in bulbectomized mice.

Pilar-Cuellar F, Castro E, Bretin S, Mocaer E, Pazos Á, Díaz Á.

​Prog Neuropsychopharmacol Biol Psychiatry. 2019 Jul 13;93:205-213. doi: 10.1016/j.pnpbp.2019.04.005. Epub 2019 Apr 10.​

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β-Catenin Role in the Vulnerability/Resilience to Stress-Related Disorders Is Associated to Changes in the Serotonergic System.

Garro-Martínez E, Vidal R, Adell A, Díaz Á, Castro E, Amigó J, Gutiérrez-Lanza R, Florensa-Zanuy E, Gómez-Acero L, Taketo MM, Pazos Á, Pilar-Cuéllar F.

Mol Neurobiol. 2019 Dec 10. doi: 10.1007/s12035-019-01841-0. [Epub ahead of print]

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Selective up-regulation of cannabinoid CB1 receptor coupling to Go-proteins in suicide victims with mood disorders.

Mato S, Pilar-Cuéllar F, Valdizán EM, González-Maeso J, Rodríguez-Puertas R, Meana J, Sallés J, Crespo-Facorro B, Pazos Á.

​Biochem Pharmacol. 2018 Nov;157:258-265. doi: 10.1016/j.bcp.2018.08.012. Epub 2018 Aug 10.​

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The endocannabinoid system in mental disorders: Evidence from human brain studies. Biochem Pharmacol.

Ibarra-Lecue I, Pilar-Cuéllar F, Muguruza C, Florensa-Zanuy E, Díaz Á, Urigüen L, Castro E, Pazos A, Callado LF.

​2018 Nov;157:97-107. doi: 10.1016/j.bcp.2018.07.009. Epub 2018 Jul 17.

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Targeting β-Catenin in GLAST-Expressing Cells: Impact on Anxiety and Depression-Related Behavior and Hippocampal Proliferation.

​Vidal R, Garro-Martínez E, Díaz Á, Castro E, Florensa-Zanuy E, Taketo MM, Pazos Á, Pilar-Cuéllar F.

​Mol Neurobiol. 2019 Jan;56(1):553-566. doi: 10.1007/s12035-018-1100-2. Epub 2018 May 8.

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Enhanced Stress Response in 5-HT1AR Overexpressing Mice: Altered HPA Function and Hippocampal Long-Term Potentiation.

Pilar-Cuéllar F, Vidal R, Díaz Á, Garro-Martínez E, Linge R, Castro E, Haberzettl R, Fink H, Bert B, Brosda J, Romero B, Crespo-Facorro B, Pazos Á.

​ACS Chem Neurosci. 2017 Nov 15;8(11):2393-2401. doi: 10.1021/acschemneuro.7b00156. Epub 2017 Aug 18.​

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The Addiction-Related Protein ANKK1 is Differentially Expressed During the Cell Cycle in Neural Precursors.

España-Serrano L, Guerra Martín-Palanco N, Montero-Pedrazuela A, Pérez-Santamarina E, Vidal R, García-Consuegra I, Valdizán EM, Pazos A, Palomo T, Jiménez-Arriero MÁ, Guadaño-Ferraz A, Hoenicka J.

​Cereb Cortex. 2017 May 1;27(5):2809-2819. doi: 10.1093/cercor/bhw129.

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A short history of the 5-HT2C receptor: from the choroid plexus to depression, obesity and addiction treatment.

Palacios JM, Pazos A, Hoyer D.

Psychopharmacology (Berl). 2017 May;234(9-10):1395-1418. doi: 10.1007/s00213-017-4545-5. Epub 2017 Mar 7.

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Chronic citalopram administration desensitizes prefrontal cortex but not somatodendritic α2-adrenoceptors in rat brain.

Fernández-Pastor B, Ortega JE, Grandoso L, Castro E, Ugedo L, Pazos Á, Meana JJ.

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Behavioral, neurochemical and molecular changes after acute deep brain stimulation of the infralimbic prefrontal cortex.

Jiménez-Sánchez L, Linge R, Campa L, Valdizán EM, Pazos Á, Díaz Á, Adell A. Neuropharmacology. 2016 Sep;108:91-102. doi: 10.1016/j.neuropharm.2016.04.020

​https://www.ncbi.nlm.nih.gov/pubmed/?term=Behavioral%2C+neurochemical+and+molecular+changes+after+acute+deep+brain+stimulation+of+the+infralimbic+prefrontal+cor

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The absence of 5-HT4 receptors modulates depression- and anxiety-like responses and influences the response of fluoxetine in olfactory bulbectomised mice: Adaptive changes in hippocampal neuroplasticity markers and 5-HT1A autoreceptor.

Amigó J, Díaz A, Pilar-Cuéllar F, Vidal R, Martín A, Compan V, Pazos A, Castro E.

​Neuropharmacology. 2016 Dec;111:47-58. doi: 10.1016/j.neuropharm.2016.08.037. Epub 2016 Aug 30.​

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Cannabidiol induces rapid-acting antidepressant-like effects and enhances cortical 5-HT/glutamate neurotransmission: role of 5-HT1A receptors.

Linge R, Jiménez-Sánchez L, Campa L, Pilar-Cuéllar F, Vidal R, Pazos A, Adell A, Díaz Á. Neuropharmacology. 2016 Apr;103:16-26. doi: 10.1016/j.neuropharm.2015.12.017.

[PubMed]

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Small Molecule Inhibition of ERK Dimerization Prevents Tumorigenesis by RAS-ERK Pathway Oncogenes.

Herrero A, Pinto A, Colón-Bolea P, Casar B, Jones M, Agudo-Ibáñez L, Vidal R, Tenbaum SP, Nuciforo P, Valdizán EM, Horvath Z, Orfi L, Pineda-Lucena A, Bony E, Keri G, Rivas G, Pazos A, Gozalbes R, Palmer HG, Hurlstone A, Crespo P.

​Cancer Cell. 2015 Aug 10 [PubMed]

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Therapeutic antidepressant potential of a conjugated siRNA silencing the serotonin transporter after intranasal administration.

Ferrés-Coy A, Galofré M, Pilar-Cuéllar F, Vidal R, Paz V, Ruiz-Bronchal E, Campa L, Pazos Á, Caso JR, Leza JC, Alvarado G, Montefeltro A, Valdizán EM, Artigas F, Bortolozzi A.

​Mol Psychiatry. 2016 Mar;21(3):328-38. doi: 10.1038/mp.2015.80. Epub 2015 Jun 23.

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Building up careers in translational neuroscience and mental health research: Education and training in the Centre for Biomedical Research in Mental Health.

Rapado-Castro M, Pazos Á, Fañanás L, Bernardo M, Ayuso-Mateos JL, Leza JC, Berrocoso E, de Arriba J, Roldán L, Sanjuán J, Pérez V, Haro JM, Palomo T, Valdizan EM, Micó JA, Sánchez M, Arango C.

​Rev Psiquiatr Salud Ment. 2015 Apr-Jun;8(2):65-74. doi: 10.1016/j.rpsm.2014.09.003. Epub 2015 Feb 12.​

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The endocannabinoid system is altered in the post-mortem prefrontal cortex of alcoholic subjects.

Erdozain AM, Rubio M, Valdizan EM, Pazos A, Meana JJ, Fernández-Ruiz J, Alexander SP, Callado LF.

​Addict Biol. 2015 Jul;20(4):773-83. doi: 10.1111/adb.12160. Epub 2014 Jul 8.​

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Serotonin 5-HT4 receptors: A new strategy for developing fast acting antidepressants?

Vidal R, Castro E, Pilar-Cuéllar F, Pascual-Brazo J, Díaz A, Rojo ML, Linge R, Martín A, Valdizán EM, Pazos A.

​Curr Pharm Des. 2014;20(23):3751-62.

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Editorial: Future trends in the development of new antidepressant drugs.

Pazos A.

​Curr Pharm Des. 2014;20(23):3717.​

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Álvaro Díaz Martínez

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Elena Castro Fernández

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Daniel Coca De Pablo

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Eva Florensa Zanuy

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Mª Fuencisla Pilar Cuéllar

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Júlia Senserrich Guerrero

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