Authors

Carlos Vicente-Gutierrez, Nicoló Bonora, Veronica Bobo-Jimenez, Daniel Jimenez-Blasco, Irene Lopez-Fabuel, Emilio Fernandez, Charlene Josephine,Gilles Bonvento, Jose A. Enriquez, Angeles Almeida and Juan P. Bolaños.

Abstract

To satisfy its high energetic demand, the brain depends on the metabolic cooperation of various cell types. For example, astrocytic-derived lactate sustains memory consolidation by serving both as an oxidizable energetic substrate for neurons and as a signalling molecule. Astrocytes and neurons also differ in the regulation of glycolytic enzymes and in the organization of their mitochondrial respiratory chain. Unlike neurons, astrocytes rely on glycolysis for energy generation and, as a consequence, have a loosely assembled mitochondrial respiratory chain that is associated with a higher generation of mitochondrial reactive oxygen species (ROS). However, whether this abundant natural source of mitochondrial ROS in astrocytes fulfils a specific physiological role is unknown. Here we show that astrocytic mitochondrial ROS are physiological regulators of brain metabolism and neuronal function. We generated mice that inducibly overexpress mitochondrial tagged catalase in astrocytes and show that this overexpression decreases mitochondrial ROS production in these cells during adulthood. Transcriptomic, metabolomic, biochemical, immunohistochemical and behavioural analysis of these mice revealed alterations in brain redox, carbohydrate, lipid and amino acid metabolic pathways associated with altered neuronal function and mouse behaviour. We found that astrocytic mitochondrial ROS regulate glucose utilization via the pentose-phosphate pathway and glutathione metabolism, which modulates the redox status and potentially the survival of neurons. Our data provide further molecular insight into the metabolic cooperation between astrocytes and neurons and demonstrate that mitochondrial ROS are important regulators of organismal physiology in vivo.

Description

La generación mitocondrial de especies reactivas de oxígeno (ROS) en el cerebro es mucho menor en las neuronas que en los astrocitos. Nuestro trabajo pone de manifiesto la relevancia de los ROS mitocondriales astrocíticos en la coordinación del metabolismo y el estado redox cerebral, así como en la regulación de funciones superiores como la conducta animal. Estos resultados contribuyen a la consideración de nuevos factores que deberán tenerse en cuenta en la búsqueda de nuevas estrategias terapéuticas basadas en el uso de sistemas antioxidantes, como son el origen celular y el papel fisiológico de los ROS en el sistema nervioso central.

 

JPB Lab 2.jpg 1

 

REFERENCIA DEL GRUPO INVESTIGADOR

Nuestro laboratorio está interesado en comprender los mecanismos moleculares que regulan la homeostasis energética y redox en las células del sistema nervioso central. Para ello, estudiamos cultivos primarios de neuronas y astrocitos murinas, además de modelos de ratón modificados genéticamente. En particular, nos interesa investigar las proteínas y las vías de señalización diferenciales entre astrocitos y neuronas, que son responsables de la adaptación del metabolismo neural a la continua y elevada demanda energética y antioxidante impuesta por la neurotransmisión.

Descargar el artículo

Did you publish an interesting article recently?

Send it through our application form and we will contact you. Age limit: 32.

The selected articles will participate at the Award to the best article of young people of the SEBBM which will be given during SEBBM conference, that will take place at Spain (free registration, travel and accommodation).

More articles of the month

Self-Assembling ELR-Based Nanoparticles as Smart Drug-Delivery Systems Modulating Cellular Growth via Akt

15-10-2019

This work investigates the physicochemical properties and in vitro accuracy of a genetically engineered drug delivery system based on elastin-like block recombinamers. The DNA recombinant technics allowed us to create...

Read more

Structure–Function of MamC Loop and Its Effect on the *in Vitro* Precipitation of Biomimetic Magnetite Nanoparticles

01-09-2019

MamC, an integral protein of the magnetosome membrane, has recently been proposed as a strong candidate to produce biomimetic (magnetosome-like) magnetite nanoparticles that could be used as an alternative to...

Read more

Sticholysin, Sphingomyelin, and Cholesterol: A Closer Look at a Tripartite Interaction

01-08-2019

Actinoporins are a group of soluble toxic proteins that bind to membranes containing sphingomyelin (SM) and oli- gomerize to form pores. Sticholysin II (StnII) is a member of the actinoporin...

Read more

Astrocytic mitochondrial ROS modulate brain metabolism and mouse behaviour

01-07-2019

To satisfy its high energetic demand, the brain depends on the metabolic cooperation of various cell types. For example, astrocytic-derived lactate sustains memory consolidation by serving both as an oxidizable...

Read more

Glucose restriction promotes osteocyte specification by activating a PGC-1α-dependent transcriptional program

03-06-2019

Osteocytes, the most abundant of bone cells, differentiate while they remain buried within the bone matrix. This encasement limits their access to nutrients and likely affects their differentiation, a process...

Read more

ParB dynamics and the critical role of the CTD in DNA condensation unveiled by combined force-fluorescence measurements

01-05-2019

/Bacillus subtilis/ ParB forms multimeric networks involving non-specific DNA binding leading to DNA condensation. Previously, we found that an excess of the free C-terminal domain (CTD) of ParB impeded DNA...

Read more

Therapeutic targeting of HER2-CB2R heteromers in HER2-positive breast cancer

01-04-2019

Although human epidermal growth factor receptor 2 (HER2)-targeted therapies have dramatically improved the clinical outcome of HER2-positive breast cancer patients, innate and acquired resistance remains an important clinical challenge. New...

Read more

p73 regulates ependymal planar cell polarity by modulating actin and microtubule cytoskeleton

01-03-2019

Planar cell polarity (PCP) and intercellular junctional complexes establish tissue structure and coordinated behaviors across epithelial sheets. In multiciliated ependymal cells, rotational and translational PCP coordinate cilia beating and direct...

Read more

β‐RA reduces DMQ/CoQ ratio and rescues the encephalopathic phenotype in Coq9R239X mice

01-02-2019

Coenzyme Q (CoQ) deficiency has been associated with primary defects in the CoQ biosynthetic pathway or to secondary events. In some cases, the exogenous CoQ supplementation has limited efficacy. In...

Read more

Small molecule inhibits α-synuclein aggregation, disrupts amyloid fibrils, and prevents degeneration of dopaminergic neurons

02-01-2019

Parkinson's disease (PD) is characterized by a progressive loss of dopaminergic neurons, a process that current therapeutic approaches cannot prevent. In PD, the typical pathological hallmark is the accumulation of...

Read more

Protector Members