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

doi:10.1016/j.redox.2021.101917

Abrogating mitochondrial ROS in neurons or astrocytes reveals cell-specific impact on mouse behaviour

Redox Biol. 2021 May:41:101917. doi: 10.1016/j.redox.2021.101917. Epub 2021 Mar 3.

Authors

Carlos Vicente-Gutierrez¹, Nicolo Bonora², Daniel Jimenez-Blasco³, Irene Lopez-Fabuel⁴, Georgina Bates⁵, Michael P Murphy⁵, Angeles Almeida⁴, Juan P Bolaños⁶

Affiliations

¹ 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. Electronic address: barrybiotec@usal.es.
² Institute of Functional Biology and Genomics, University of Salamanca, CSIC, 37007, Salamanca, Spain.
³ 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.
⁴ 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.
⁵ MRC Mitochondrial Biology Unit & Department of Medicine, University of Cambridge, Cambridge, CB2 0XY, United Kingdom.
⁶ 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. Electronic address: jbolanos@usal.es.

Abstract

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.

Keywords: Astrocyte; In vivo; Mitochondria; Neuron; ROS; Signallling.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Astrocytes* / metabolism
Cells, Cultured
Mice
Mitochondria*
Neurons
Reactive Oxygen Species / metabolism

Substances

Reactive Oxygen Species

Grants and funding

MC_UU_00015/3/MRC_/Medical Research Council/United Kingdom