Abrogating mitochondrial ROS in neurons or astrocytes reveals cell-specific impact on mouse behaviour
Carlos Vicente-Gutierrez,
Nicolo Bonora,
Daniel Jimenez-Blasco,
Irene Lopez-Fabuel,
Georgina Bates,
Michael P. Murphy,
Angeles Almeida,
Juan P. Bolaños
Affiliations
Carlos Vicente-Gutierrez
Institute of Functional Biology and Genomics, University of Salamanca, CSIC, 37007, Salamanca, Spain; Centro de Investigación Biomédica en Red Sobre Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III, Madrid, Spain; Institute of Biomedical Research of Salamanca, University Hospital of Salamanca, University of Salamanca, CSIC, 37007, Salamanca, Spain; Corresponding author. Institute of Functional Biology and Genomics, C/ Zacarias Gonzalez, 2, 37007, Salamanca, Spain.
Nicolo Bonora
Institute of Functional Biology and Genomics, University of Salamanca, CSIC, 37007, Salamanca, Spain
Daniel Jimenez-Blasco
Institute of Functional Biology and Genomics, University of Salamanca, CSIC, 37007, Salamanca, Spain; Centro de Investigación Biomédica en Red Sobre Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III, Madrid, Spain; Institute of Biomedical Research of Salamanca, University Hospital of Salamanca, University of Salamanca, CSIC, 37007, Salamanca, Spain
Irene Lopez-Fabuel
Institute of Functional Biology and Genomics, University of Salamanca, CSIC, 37007, Salamanca, Spain; Institute of Biomedical Research of Salamanca, University Hospital of Salamanca, University of Salamanca, CSIC, 37007, Salamanca, Spain
Georgina Bates
MRC Mitochondrial Biology Unit & Department of Medicine, University of Cambridge, Cambridge, CB2 0XY, United Kingdom
Michael P. Murphy
MRC Mitochondrial Biology Unit & Department of Medicine, University of Cambridge, Cambridge, CB2 0XY, United Kingdom
Angeles Almeida
Institute of Functional Biology and Genomics, University of Salamanca, CSIC, 37007, Salamanca, Spain; Institute of Biomedical Research of Salamanca, University Hospital of Salamanca, University of Salamanca, CSIC, 37007, Salamanca, Spain
Juan P. Bolaños
Institute of Functional Biology and Genomics, University of Salamanca, CSIC, 37007, Salamanca, Spain; Centro de Investigación Biomédica en Red Sobre Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III, Madrid, Spain; Institute of Biomedical Research of Salamanca, University Hospital of Salamanca, University of Salamanca, CSIC, 37007, Salamanca, Spain; Corresponding author. Institute of Functional Biology and Genomics, C/ Zacarias Gonzalez, 2, 37007, Salamanca, Spain.
Cells naturally produce mitochondrial reactive oxygen species (mROS), but the in vivo pathophysiological significance has long remained controversial. Within the brain, astrocyte-derived mROS physiologically regulate behaviour and are produced at one order of magnitude faster than in neurons. However, whether neuronal mROS abundance differentially impacts on behaviour is unknown. To address this, we engineered genetically modified mice to down modulate mROS levels in neurons in vivo. Whilst no alterations in motor coordination were observed by down modulating mROS in neurons under healthy conditions, it prevented the motor discoordination caused by the pro-oxidant neurotoxin, 3-nitropropionic acid (3-NP). In contrast, abrogation of mROS in astrocytes showed no beneficial effect against the 3-NP insult. These data indicate that the impact of modifying mROS production on mouse behaviour critically depends on the specific cell-type where they are generated.
