Institut de Neurociències (INc) - UAB Barcelona

International consensus to spur the study of astrocytes in diseases of the nervous system

International consensus to spur the study of astrocytes in diseases of the nervous system

Dr. Elena Galea, ICREA researcher at our Institute, has led a study, published in Nature Neuroscience, in which more than 80 international scientists have worked collectively to clarify definitions, nomenclatures, controversies, and upcoming goals in astrocytes research. The article represents a theoretical breakthrough that will accelerate the acquisition of knowledge about the involvement of these cells in diseases of the central nervous system. Read the article

16/02/2021

Ramon y Cajal discovered that astrocytes, cells responsible for an optimal brain environment so that all functions can be performed, change shape when there is an infection, injury, or disease of the central nervous system. More than a hundred years later, many doubts are still unsolved about the implications of these morphological changes and the role astrocytes play in central nervous system diseases.

Research in this field has accelerated in recent years, with new researchers providing new techniques, approaches, and hypotheses. Therefore, some experts have considered an urgent need to unify the nomenclature used and refine the concepts: many terms related to astrocytes have been understood in different ways by different experts.

An international team of researchers has agreed upon guidelines and nomenclatures. Elena Galea, ICREA at INC-UAB and a member of the Consolidated Research Group of Dementias at the Hospital de Sant Pau, together with Carole Escartín, professor at the University of Paris-Saclay; Michael V. Sofroniew, of the University of California, and Alexei Verkhratsky, of the University of Manchester, have worked on a consensus document, approved by more than 80 experts, published in Nature Neuroscience. "Reaching such a large agreement has taken a year of work, in which circles of revision and discussion of the text have been established, under our coordination", explains Elena Galea.

The study unifies all the names that refer to reactive astrocytes, reviews the laboratory techniques currently in use, and dispels false myths, such as the existence of ‘good’ and ‘bad’ astrocytes. It also proposes a paradigm change, focusing preferably on the analysis of molecular and functional alterations, instead of the morphological ones, as has been the case so far.

"Currently, most of the treatments for nervous system diseases are targeted to neurons. This work is essential because it will stimulate international collaborations, and promote cutting-edge molecular techniques and statistical analysis to understand astrocytes’ functions in brain circuits. We also want to determine astrocytes’ involvement in central nervous system diseases and address unexplored therapeutic niches, such as therapies targeting astrocytes”, concludes Dr. Galea, who expresses her gratitude to the INc, in particular to the Unitat de Bioquímica, “for their unwavering faith in my scientific capabilities, which have facilitated that, for the first time, a member of the INc sign an article in Nature Neuroscience as a corresponding author”. Read the article



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New brain alterations induced by main genetic risk factor in Alzheimer's disease discovered

New brain alterations induced by main genetic risk factor in Alzheimer's disease discovered

The Apolipoprotein gene (APOE) can be given in three variants in humans: E2, E3 and E4. APOE4 can cause structural and functional alterations to the brain and is the principal genetic risk in the development of the most common type of Alzheimer's disease, called sporadic, which appears in 99% of cases (the remaining 1% corresponds to familial Alzheimer's).

Researchers from the INc-UAB and the Department of Biochemistry and Molecular Biology at the UAB, coordinated by Roser Masgrau and Elena Galea, who is also an ICREA researcher, have now published a study in the journal Molecular Neurodegeneration that adds new data on the brain functions of APOE and the mechanisms by which the E4 variant could be key to the development of the disease.

The study demonstrates that APOE4 causes alterations in the lysosomes of astrocytes. Lysosomes are cellular organelles with diverse functions, such as the digestion of substances that the cell does not need anymore. These alterations in the lisosomes increase calcium signals, the main system by which the cell responds to stimuli and impede their modulation by lipids. Among other processes, the calcium signaling pathway allows astrocytes to regulate neuronal connections, and therefore mechanisms of learning and memory. Previous studies in mice models described that beta-amyloid plates affect the calcium signaling. In this study, researchers demonstrate that malfunctions in calcium signaling appear in astrocytes long before amyloid plaques accumulation and that APOE4 plays a very important role in this dysfunction.

The research also shows that alterations in calcium signals appear in female mice expressing APOE3 or APOE4 variants, though the age or lipid regulation could imply a positive evolution for females with E3, according to the hypothesis of the researchers.

"The article corroborates the need to keep in mind gender differences when studying APOE4 and Alzheimer's disease", explains Raquel Larramona, PhD student at the INc-UAB when the study was carried out, and first author of the article.

"Our study has two clear therapeutic implications: on the one hand, it provides support to those pharmacological interventions focussed on replacing intracellular calcium signaling in APOE4 patients with cognitive alterations, and on the other, it opens the door to new medical therapies to slow the progression of Alzheimer's in patients with the APOE4 variant", adds Dr. Masgrau.

The study was conducted with the involvement of researchers from the Harvard Medical School (USA), the Vall d'Hebron Research Institute (VHIR), the Cajal Institute in Madrid, the University of Valladolid, the University of Seville, the University of Malaga, the University of Huelva, the CSIC and the CIBERNED. La Marató de TV3 Foundation has been the main source of funding.

Read the article

The H2020 project QSPainRelief awarded by the European Commission

The H2020 project QSPainRelief awarded by the European Commission

The QSPainRelief project "Effective combinational treatment of chronic pain in individual patients by an innovative quantitative systems pharmacology pain relief approach", which includes the participation of Dr. Jesús Giraldo’s team (Institute for Neurosciences and Biostatistics Unit of the School of Medicine), has been funded from the European Commission.

This  project will attempt to solve a crucial problem since about 20% of Europeans suffer from chronic pain and current therapies are not effective in many cases. Around 60% of patients do not reach enough relief from traditional painkillers, which in turn can lead to several adverse effects.

The QSPainRelief project addresses the problem of chronic pain by identifying new drug combinations that are expected to increase analgesic efficacy while reducing side effects. To do this, quantitative systems pharmacology and computational modeling will be used. The best combinations will be validated in animal models and clinical studies.

The QSPainRelief project will receive more than € 6 million in funding for 5 years through the H2020 program. The project is a collaboration between 9 research institutions from 6 different countries, including the UAB, starting January 1, 2020.

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