Inglés (Estados Unidos)

Mª Fuencisla Pilar Cuéllar (IP)

IBBTEC. c/ Albert Einstein, 22; 39011 Santander
mariafuencisla.pilar@unican.es
942 206 860
Neurobiological Basis of the Mechanism of Action of Drugs acting at the Central Nervous System
Principal Investigator
Neuropharmacology
Department of Cell & Molecular Signalling

Fuencisla Pilar is Assistant Professor of Pharmacology and member of the Research Group "Neurobiological Bases of the Mechanism of Action of Drugs acting on the Central Nervous System" 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), led by Professor Ángel Pazos. Dr. Pilar obtained the Bachelor's Degree in Biological Sciences from the University of León in 1998 and the Doctorate from the same University in 2006 in the field of neuroscience. In 2007, she joined Prof. Pazos' group (University of Cantabria, UC), as a CIBERSAM researcher. During that period, she focused her research on the role of modulation of 5-HT_2A receptors in the treatment of depression, in addition to the involvement of neuroplastic processes in the antidepressant effect. In 2011, she carried out a postdoctoral stay in the Molecular Pharmacology group of Dr. González-Maeso (Mount Sinai School of Medicine, New York, USA), studying of the implication of the 5-HT_2A/mGlu₂ dimer in the neurobiology of schizophrenia. Currently, her research activity is focused on the study of the mechanism of action of fast-acting antidepressant drugs such as cannabidiol and ketamine, focusing on aspects related to neuroplasticity and neuroinflammation. She is co-IP of two national projects SAF2015-67457-R and RTI2018-097534-B-I00. Regarding the academic activity, she teaches Pharmacology in the Degree of Medicine and the "Master's Degree in Initiation in Research in Mental Health" (CIBERSAM) and "Master's Degree in Molecular Biology and Medicine" (UC/UPV). She is also secretary of the Bioethics Committee of the UC.

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:

Modulation of neuroproliferation and neuroplasticity pathways as a mechanism of action of antidepressants.
Involvement of the aminergic and cannabinoid systems in depression.
Preclinical evaluation of potential antidepressants in animal models.
Involvement of neuroinflammation in depression and antidepressant actions.
Mechanism of action of molecules with rapid antidepressant effect.

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

ER stress in mouse serotonin neurons triggers a depressive phenotype alleviated by ketamine targeting eIF2α signaling

Miquel-Rio L, Sarriés-Serrano U, Sancho-Alonso M, Florensa-Zanuy E, Paz V, Ruiz-Bronchal E, Manashirov S, Campa L, Pilar-Cuéllar F, Bortolozzi A.

iScience. 2024 Apr 18;27(5):109787. eCollection 2024 May 17.

Brain matrix metalloproteinase-9 activity is altered in the corticosterone mouse model of depression

Breviario S, Senserrich J, Florensa-Zanuy E, Garro-Martínez E, Díaz Á, Castro E, Pazos Á, Pilar-Cuéllar F.

Prog Neuropsychopharmacol Biol Psychiatry. 2023 Jan 10;120:110624.

Molecular Signaling Mechanisms for the Antidepressant Effects of NLX-101, a Selective Cortical 5-HT 1A Receptor Biased Agonist

Cabanu S, Pilar-Cuéllar F, Zubakina P, Florensa-Zanuy E, Senserrich J, Newman-Tancredi A, Adell A.

Pharmaceuticals (Basel). 2022 Mar 10;15(3):337.

mTOR Knockdown in the Infralimbic Cortex Evokes A Depressive-like State in Mouse

Garro-Martínez E, Fullana MN, Florensa-Zanuy E, Senserrich J, Paz V, Ruiz-Bronchal E, Adell A, Castro E, Díaz Á, Pazos Á, Bortolozzi A, Pilar-Cuéllar F.

Int J Mol Sci. 2021 Aug 12;22(16):8671. doi: 10.3390/ijms22168671.

Structural connectivity and subcellular changes after antidepressant doses of ketamine and Ro 25-6981 in the rat: an MRI and immuno-labeling study

Pascual-Antón R, Blasco-Serra A, Muñoz-Moreno E, Pilar-Cuéllar F, Garro-Martínez E, Florensa-Zanuy E, López-Gil X, Campa VM, Soria G, Adell A.

Brain Struct Funct. 2021 Aug 7. doi: 10.1007/s00429-021-02354-0.

Structural connectivity and subcellular changes after antidepressant doses of ketamine and Ro 25-6981 in the rat

Pascual-Antón R, Blasco-Serra A, Muñoz-Moreno E, Pilar-Cuéllar F, Garro-Martínez E, Florensa-Zanuy E, López-Gil X, Campa VM, Soria G, Adell A.

Brain Struct Funct. 2021 Nov;226(8):2603-2616.

5-HT 4 Receptors Are Not Involved in the Effects of Fluoxetine in the Corticosterone Model of Depression

Amigo J, Garro-Martinez E, Vidal Casado R, Compan V, Pilar-Cuéllar F, Pazos A, Díaz A, Castro E.

ACS Chem Neurosci. 2021 Jun 2;12(11):2036-2044. doi: 10.1021/acschemneuro.1c00158. Epub 2021 May 11.

Cannabidiol antidepressant-like effect in the lipopolysaccharide model in mice: Modulation of inflammatory pathways

Florensa-Zanuy E, Garro-Martínez E, Adell A, Castro E, Díaz Á, Pazos Á, Mac-Dowell KS, Martín-Hernández D, Pilar-Cuéllar F.

Biochem Pharmacol. 2021 Mar;185:114433. doi: 10.1016/j.bcp.2021.114433. Epub 2021 Jan 26.

Increased vulnerability to impulsive behavior after streptococcal antigen exposure and antibiotic treatment in rats.

Santiago Mora, Elena Martín-González, Ángeles Prados-Pardo, José Joaquín Moreno-Casco, María José López-López, Fuencisla Pilar-Cuellar, Elena Castro, Álvaro Díaz, Pilar Flores, Margarita Moreno

Brain Behav Immun. 2020 Aug 13:S0889-1591(20)30083-0. doi: 10.1016/j.bbi.2020.08.010. Online ahead of print.

Opioid receptors mRNAs expression and opioids agonist-dependent G-protein activation in the rat brain following neuropathy

Llorca-Torralba M, Pilar-Cuéllar F, da Silva Borges G, Mico JA, Berrocoso E.

Neuropsychopharmacol Biol Psychiatry. 2020 Apr 20;99:109857

Dopaminergic control of ADAMTS2 expression through cAMP/CREB and ERK: molecular effects of antipsychotics

Ruso-Julve F, Pombero A, Pilar-Cuéllar F, García-Díaz N, Garcia-Lopez R, Juncal-Ruiz M, Castro E, Díaz Á, Vazquez-Bourgón J, García-Blanco A, Garro-Martinez E, Pisonero H, Estirado A, Ayesa-Arriola R, López-Giménez J, Mayor F Jr, Valdizán E et al.

Transl Psychiatry. 2019 Nov 18;9(1):306. doi: 10.1038/s41398-019-0647-7.

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.

Effect of cannabis on weight and metabolism in first-episode non-affective psychosis: Results from a three-year longitudinal study.

Vázquez-Bourgon J, Setién-Suero E, Pilar-Cuéllar F, Romero-Jiménez R, Ortiz-García de la Foz V, Castro E, Crespo-Facorro B.

J Psychopharmacol. 2019 Mar;33(3):284-294. doi: 10.1177/0269881118822173. Epub 2019 Jan 31.

Opioid Activity in the Locus Coeruleus Is Modulated by Chronic Neuropathic Pain.

Llorca-Torralba M, Pilar-Cuéllar F, Bravo L, Bruzos-Cidon C, Torrecilla M, Mico JA, Ugedo L, Garro-Martínez E, Berrocoso E.

Mol Neurobiol. 2019 Jun;56(6):4135-4150. doi: 10.1007/s12035-018-1361-9. Epub 2018 Oct 3.

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.

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.

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.

Signaling pathways responsible for the rapid antidepressant-like effects of a GluN2A-preferring NMDA receptor antagonist.

Gordillo-Salas M, Pilar-Cuéllar F, Auberson YP, Adell A.

Transl Psychiatry. 2018 Apr 18;8(1):84. doi: 10.1038/s41398-018-0131-9.

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.

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.

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]

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. Epub 2015 Dec 19.

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.

Increased SP4 and SP1 transcription factor expression in the postmortem hippocampus of chronic schizophrenia.

Pinacho R, Valdizán EM, Pilar-Cuellar F, Prades R, Tarragó T, Haro JM, Ferrer I, Ramos B.

J Psychiatr Res. 2014 Nov;58:189-96. doi: 10.1016/j.jpsychires.2014.08.006. Epub 2014 Aug 19.

TGF-β and opioid receptor signaling crosstalk results in improvement of endogenous and exogenous opioid analgesia under pathological pain conditions.

Lantero A, Tramullas M, Pílar-Cuellar F, Valdizán E, Santillán R, Roques BP, Hurlé MA.

J Neurosci. 2014 Apr 9;34(15):5385-95. doi: 10.1523/JNEUROSCI.4405-13.2014.

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.

Signaling pathways involved in antidepressant-induced cell proliferation and synaptic plasticity.

Pilar-Cúellar F, Vidal R, Díaz A, Castro E, dos Anjos S, Vargas V, Romero B, Valdizán EM.

Curr Pharm Des. 2014;20(23):3776-94.

Ángel Pazos Carro (IP)

Elena Castro Fernández

Álvaro Díaz Martínez

Júlia Senserrich Guerrero

Martina Serrano Díaz

IBBTEC

Instituto de Biomedicina y Biotecnología de Cantabria.
PCTCAN - Cl. Albert Einstein, 22
39011 Santander
ibbtec@unican.es

Mª Fuencisla Pilar Cuéllar (IP)

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

Research lines

Funding

ER stress in mouse serotonin neurons triggers a depressive phenotype alleviated by ketamine targeting eIF2α signaling

Brain matrix metalloproteinase-9 activity is altered in the corticosterone mouse model of depression

Molecular Signaling Mechanisms for the Antidepressant Effects of NLX-101, a Selective Cortical 5-HT 1A Receptor Biased Agonist

mTOR Knockdown in the Infralimbic Cortex Evokes A Depressive-like State in Mouse

Structural connectivity and subcellular changes after antidepressant doses of ketamine and Ro 25-6981 in the rat: an MRI and immuno-labeling study

Structural connectivity and subcellular changes after antidepressant doses of ketamine and Ro 25-6981 in the rat

5-HT 4 Receptors Are Not Involved in the Effects of Fluoxetine in the Corticosterone Model of Depression

Cannabidiol antidepressant-like effect in the lipopolysaccharide model in mice: Modulation of inflammatory pathways

Increased vulnerability to impulsive behavior after streptococcal antigen exposure and antibiotic treatment in rats.

Opioid receptors mRNAs expression and opioids agonist-dependent G-protein activation in the rat brain following neuropathy

Dopaminergic control of ADAMTS2 expression through cAMP/CREB and ERK: molecular effects of antipsychotics

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

Effect of cannabis on weight and metabolism in first-episode non-affective psychosis: Results from a three-year longitudinal study.

Opioid Activity in the Locus Coeruleus Is Modulated by Chronic Neuropathic Pain.

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

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

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

Signaling pathways responsible for the rapid antidepressant-like effects of a GluN2A-preferring NMDA receptor antagonist.

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

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.

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

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

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

Increased SP4 and SP1 transcription factor expression in the postmortem hippocampus of chronic schizophrenia.

TGF-β and opioid receptor signaling crosstalk results in improvement of endogenous and exogenous opioid analgesia under pathological pain conditions.

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

Signaling pathways involved in antidepressant-induced cell proliferation and synaptic plasticity.

Ángel Pazos Carro (IP)

Elena Castro Fernández

Álvaro Díaz Martínez

Júlia Senserrich Guerrero

Martina Serrano Díaz

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