Cannabinoid receptor mediated signaling

This line of research is aimed at the pharmacological and functional characterization of the CB1 receptor by radioligand and agonist-stimulated GTPγS binding techniques. These techniques allow to determine receptors density in synaptosomes obtained from brain tissue, as well as G-protein coupling in samples of animal or human origin.

In the same line of work, thanks to the stable collaboration with the group of the Department of Analytical Chemistry of the UPV/ EHU led by Arantza Goicolea PhD, the research group has implemented techniques for the determination of endogenous cannabinoids in brain tissue using mass spectrometry and liquid chromatography, which allows studying the levels of these compounds in the brain in both physiological and pathological conditions.

During the last years, by means of brain tissue fractionation and Western blotting techniques, we are carrying out studies aimed at determining the subcellular, subsynaptic and membrane subdomain (“raft” vs. “non-raft”) distribution CB1 receptors, of the elements involved in CB1-mediated signalling through G proteins as well as of the enzymes involved in the synthesis and degradation of endocannabinoids. At present, a large part of these works are being carried out in the context of a project directed by Pedro Grandes PhD founded by the Basque Government in the 2018 call (“Ayudas para apoyar las actividades de investigación del Sistema Universitario Vasco”).

Phospholipase C-β1 signaling in neuronal differentiation and survival

During the last years, our group has advanced in two lines of research that converge in the search for the role that nuclear phospholipase C-β1 (PLCβ1) dependent signaling has in neuronal differentiation and survival. On the one hand, we have observed that of PLCβ1 expression is necessary for neuronal differentiation induced in the human cell line NT2 cells. In addition, PLCβ1 overexpression is sufficient to induce differentiation. On the other hand, we have shown that the enzymes PLCβ1 and diacylglycerol lipase α (DAGLα) are located in discrete domains of the neuronal nucleus and that they work in concert for the production of the endocannabinoid 2-arachidonylglycerol (2-AG).

Over the next few years, our research line is built on the basis of the importance of PLCβ1 in neuronal differentiation and the possible neuroprotective role of 2-AG or glycerol prostaglandin esters derived from it. Therefore, we propose to study the mechanisms dependent on the nuclear PLCβ1/DAGLα/2-AG signaling axis in neuronal differentiation and survival.

Development and characterization of molecular footprint polymers as tools for protein analysis

Currently, in collaboration with the group of the Department of Analytical Chemistry of the UPV/EHU led by Dr. Arantza Goicolea, we participate in a multidisciplinary project funded by the Spanish “Ministerio de Economía, Industria y Competitividad” for the development and characterization of synthetic Molecularly Imprinted Polymers (MIPs) with affinity and specificity features for mammalian proteins comparable to those of antibodies. The ultimate goal is the substitution of antibodies for this type of nanoparticles with analytical purposes in a variety of approaches, such as immunohistochemistry/immunofluorescence, immunoprecipitation, Western blot assays or protein determination by ELISA. MIPs offer several clear advantages over antibodies and have great translational potential in the biotechnological and health fields, given the high demand for molecules capable of recognizing proteins in a highly selective way. Among these advantages, it is worth highlighting the possibility of generating MIPs against any peptide sequence, avoiding the limitations that antibodies require in terms of the antigenic capacity of said sequences. Also, these molecules are great stable. MIPs allow the replacement of animals necessary for the generation of antibodies, thus avoiding ethical inconveniences as well as the high cost of production.

Currently, the group is composed of five PhD professors with teaching and research activities at the Faculty of Pharmacy of the UPV/EHU. Two of them belong to the Department of Neurosciences, while three others are part of the Department of Pharmacology. The group is led by Joan Sallés, belonging to the Department of Pharmacology and also has three PhD students, all scholarship holders in competitive calls.

Miembros del grupo adscritos al Departamento de Neurociencias

• Gontzal García del Caño (Profesor Titular de Universidad).
• Imanol González Burguera (Profesor Adjunto).

• Peñasco S, Rico-Barrio I, Puente N, Fontaine CJ, Ramos A, Reguero L, Gerrikagoitia I, de Fonseca FR, Suarez J, Barrondo S, Aretxabala X, García del Caño G, Sallés J, Elezgarai I, Nahirney PC, Christie BR, Grandes P (2020). Intermittent ethanol exposure during adolescence impairs cannabinoid type 1 receptor-dependent long-term depression and recognition memory in adult mice. Neuropsychopharmacology, 45: 309-318. DOI: 10.1038/s41386-019-0530-5.

• González-Burguera I, Ricobaraza A, Aretxabala X, Barrondo S, García Del Caño G, López de Jesús M, Sallés J (2016). Highly efficient generation of glutamatergic/cholinergic NT2-derived postmitotic human neurons by short-term treatment with the nucleoside analogue cytosine β-D-arabinofuranoside. Stem Cell Research, 16: 541-551. DOI: 10.1016/j.scr.2016.02.038.

• Scarlata S, Garwain O, Williams L, González-Burguera I, Rosati B, Sahu S, Guo Y, Philip F, Golebiewska U (2016). Phospholipase Cβ connects G protein signaling with RNA interference. Advances in Biological Regulation, 61:51-67. DOI: 10.1016/j.jbior.2015.11.006.

• Agirre M, Ojeda E, Zarate J, Puras G, Grijalbo S, Eritja R, García del Caño G, Barrondo S, González-Burguera I, López de Jesús M, Sallés J, Pedraz JL (2015). New insights into gene delivery to human neuronal precursor NT2 cells: a comparative study between lipoplexes, nioplexes and polyplexes. Molecular Pharmaceutics, 12: 4056-4066. DOI: 10.1021/acs.molpharmaceut.5b00496.

• García del Caño G, Aretxabala X, González-Burguera I, Montaña M, López de Jesús M, Barrondo S, Barrio R, Sampedro C, Goicolea MA, Sallés J (2015). Nuclear diacylglycerol lipase-α in rat brain cortical neurons: evidence of 2-arachidonoylglycerol production in concert with phospholipase C-β activity. Journal of Neurochemistry, 132: 489-503. DOI: 10.1111/jnc.12963.

• Borrega L, Saumell M, Isasti A, Aretxabala X, Gonzalez-Burguera G, López de Jesús M, García del Caño G, SallésJ, Barrondo S (2019). Ketaminaren eragin antidepresiboak. Ekintza mekanismo berriak farmako antidepresiboen bilaketarako. Ekaia, 35: 41-56. ISSN: 0214-9001.

Modulación del daño cerebral por receptores de cannabinoides localizados en dominios subcelulares específicos en un modelo de epilepsia. Gobierno Vasco. Departamento de Educación. Ayudas para apoyar las actividades de investigación del Sistema Universitario Vasco. (Ref. IT1230-19).

• Periodo de ejecución: 01/01/2019 - 31/12/2021.
• Investigador principal: Pedro Rolando Grandes Moreno (UPV/EHU).
• Cuantía de la subvención: 179.200 €
• Número de investigadores participantes: 20

Sensores basados en polímeros de huella molecular para su aplicación al estudio de receptores acoplados a proteínas G. Ministerio de Economía y Competitividad – MINECO Programa Estatal de Investigación, Desarrollo e Innovación orientada a los Retos de la Sociedad (Ref. CTQ2017-85686-R).

• Periodo de ejecución: 01/01/2018 - 31/12/2020.
• Investigadores principales: Joan Sallés Alvira (UPV/EHU) y María Aranzazu Goicolea Altuna (UPV/EHU).
• Cuantía de la subvención: 61.710 €
• Número de investigadores participantes: 10

La colaboración técnica en materia de caracterización in vitro de los efectos celulares de exosomas derivados de plasma humano rico en plaquetas. Contrato OTRI entre la UPV/EHU y la Unidad de Cirugía Artroscópica, S. L.

• Periodo de ejecución: 01/08/2018 - 31/10/2018.
• Investigador Principal: Joan Sallés Alvira (UPV/EHU).
• Cuantía de la subvención (IVA no incluido): 8.677,69 €
• Número de investigadores participantes: 4

La colaboración técnica en materia de obtención y caracterización de exosomas derivados de plasma humano rico en plaquetas. Contrato OTRI entre la UPV/EHU y la Unidad de Cirugía Artroscópica, S. L. (Ref. 2018.0017).

• Periodo de ejecución: 30/11/2017 - 30/04/2018.
• Investigador Principal: Joan Sallés Alvira (UPV/EHU).
• Cuantía de la subvención (IVA no incluido): 8.677,69 €
• Número de investigadores participantes: 4

La colaboración técnica en materia de ensayos in vivo de muestras de plasma rico en plaquetas. Contrato OTRI entre la UPV/EHU y la Unidad de Cirugía Artroscópica, S. L. (Ref. 2017.0171).

• Periodo de ejecución: 31/03/2017 - 30/09/2018.
• Investigador Principal: Joan Sallés Alvira (UPV/EHU).
• Cuantía de la subvención (IVA no incluido): 17.588,56 €
• Número de investigadores participantes: 4

2-Arakidonilglizerol endokannabinoidearen sintesi- eta degradazio-makineria neuronaren nukleoan: Diazilglizerol Lipasa alfa-ren konpartimentazioa eta aktibitate entzimatikoa.

• Estudiante: Xabier Arechavala Rodríguez. Sobresaliente Cum Laude.
• Directores: Gontzal García del Caño y Sergio Barrondo Lacarra.
• Curso de defensa: 2017-2018.

Señalización a través de las isoformas de fosfolipasa C-β1 en los procesos de diferenciación neuronal.

• Estudiante: Amaia Isasti Iribar.
• Directores: Gontzal García del Caño y Maider López de Jesús.
• Curso de defensa: En curso.

Ingurune aberastuaren eragina C57BL6J saguen CB1 hartzaileetan nerabezaroan botiloi ohituraren ondoren.

• Máster: Máster en Neurociencias (UPV/EHU).
• Estudiante: Maitane Serrano Murguia.
• Co-directores: Gontzal García del Caño e Irantzu Rico Barrio.
• Curso de defensa: 2018-2019.

Trabajos fin de grado (últimos 2 años)

Alzheimerraren tratamenduaren aurrerapenak: immunoterapia

• Grado: Grado en Farmacia (UPV/EHU).
• Estudiante: Paula Mayor Zapatero.
• Co-directores: Gontzal García del Caño y Maider López de Jesús.
• Curso de defensa: 2018-2019.

siRNA terapia genikoa: etorkizun handiko estrategia terapeutiko berria

• Grado: Grado en Farmacia (UPV/EHU).
• Estudiante: Maitane Lerga Sola.
• Directores: Imanol Gonzalez Burguera y Maider López de Jesús.
• Curso de defensa: 2018-2019.