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Neurotransmission and Purinergic Signalling

Neurotransmission and Purinergic Signalling

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PRINCIPAL INVESTIGATOR

Garcia Delicado, Esmerilda
esmerild@vet.ucm.es
Tel. +34 913943894
ADDRESS

Department of Biochemistry and Molecular Biology IV

Faculty of Veterinary Medicine, UCM
Pl. de Ramón y Cajal, s/n, 28040 Madrid

Group information

The main focus of research is the study of nucleotide receptor signalling in the central nervous system and its role in processes such as neuronal survival, differentiation, and regeneration. Nucleotides regulate a wide variety of functions by activating ionotropic (P2X) and metabotropic (P2Y) receptors that are ubiquitously distributed in different populations of neurons and astrocytes. Recent work has described the neuroprotective role of P2X7 and P2Y13 receptors in these neural models against different apoptotic stimuli, and enhancing the protective effects of neurotrophic factors, such as BDNF, by virtue of their coupling to different signalling proteins, MAP kinases, and GSK3. This signalling is also involved in the transcriptional regulation of the P2X7 receptor. A new line of research of the group focuses on the regulatory mechanisms of adult neurogenesis and the involvement of purinergic receptors in this process.

Review

Degree (1982) and PhD in Biology with Extraordinary Prize (1987) from the University of Murcia. She is currently Professor of Biochemistry and Molecular Biology at the Complutense University of Madrid.

She started her research career as a student intern at the Interfaculty Department of Biochemistry of the University of Murcia, where she completed her thesis under the supervision of Dr. Juan Carmelo Gómez Fernández, and most of the experimental work for her doctoral thesis, thanks to a grant from the FIS. In 1986 he moved to the Faculty of Veterinary Medicine of the Complutense University of Madrid together with his thesis supervisor, Dr. Mª Teresa Miras Portugal, where he has developed his entire teaching and research career.

Her research has focused on the study of different stages of extracellular nucleotide-mediated signalling. She contributed to the characterisation of the nucleoside transporter in different neural models, a key step in the recovery of intracellular levels of adenosine, the end product of extracellular nucleotide hydrolysis. Studies in chromaffin cells showed that the facilitated diffusion transporter (SLC29) was regulated by phosphorylation-dephosphorylation processes as was later demonstrated for other neurotransmitter transporters. In recent years, the research line has mainly focused on the study of nucleotide receptors and their implications in neuroprotection processes in order to identify new therapeutic targets.

He has participated in more than 30 national and European research projects.

He has supervised 9 doctoral theses and numerous dissertations and dissertations.

Total publications: 58 h-index: 23.74. Total citations: 1,377 (WOS).

Six-year research periods awarded: 5 (last six-year period: 2011-2016).

Five-year teaching periods awarded: 6.

ORCID code. 0000-0001-6281-0816.

Research ID: L-6992-2014.

SCOPUS: 6701879595

Strategic objectives

To study of the differential signalling of nucleotide receptors, especially the ionotropic receptor P2X7, in neurons and astrocytes from different areas of the brain, cerebellum, cortex, and hippocampus.
To study of the effect of nucleotides on the survival and differentiation of neuronal and glial populations, and analysis of the intracellular mechanisms responsible for these effects. We will focus on the MAP kinase cascade and the GSK3 protein, as well as induced genes that could mediate both protective and reparative responses.
Interaction of nucleotide receptors with other survival factors, such as growth factors and neurotrophins.
To study of growth factors as regulators of nucleotide receptor gene expression, especially the P2X7 receptor.
To study of the role of purinergic receptors in adult neurogenesis in the murine brain in the subependymal zone (SEZ) of the lateral ventricle and in the granular zone of the dentate gyrus (SGZ). Analysis of the expression of receptors and ectoenzymes and their role in the progression and differentiation of different neural progenitor lineages.
Study of nucleotide receptor-coupled signalling in macrophages and its role in inflammatory function. Interaction with other inflammatory signals.

Lines of research

Signalling and physiology of nucleotide receptors in populations of neurons and astrocytes in the cerebellum, cortex, and hippocampus.
Role of nucleotide receptors in neuroprotection and neuroregeneration.
Interaction of nucleotide receptors with other neurotransmitter and growth factor systems.
Transcriptional regulation of nucleotide receptors.
Regulatory mechanisms of adult neurogenesis.
Role of nucleotide receptors in inflammation and neuropathic pain.
Pharmacological and functional characterisation of nicotinic receptors in the adrenal medulla of KO and KI mice for the alpha9 nicotinic receptor.
Mechanisms involved in stress-induced plasticity of alpha9 nicotinic receptors in chromaffin cells. Involvement in exocytosis
Identification and functional characterisation of alpha9 nicotinic receptors in dorsal root ganglion neurons of the rat spinal cord in models of neuropathic pain (partial ligation and chronic constriction of the rat sciatic nerve).
Involvement of P2X7 receptors in the propagation of cytosolic calcium waves in astrocytes (cerebral cortex and cerebellum) in culture and in rat and mouse brain slices: Analysis of interspecific differences.
P2X7 receptor regulation of gliotransmitter exocytosis in cultured rat and mouse brain astrocytes.
Regulation of astrocyte P2X7 receptor activity by redox state.
Regulation of connexin and glutamate transporter activity by the P2X7 receptor.
Study of the involvement of the purinergic system in the development of neurodegenerative diseases. Search for new therapeutic targets.
Role of nucleotide receptors in neuronal differentiation, involvement in axonal and dendritic development.