Journal article

Glutathione deficit impairs myelin maturation: relevance for white matter integrity in schizophrenia patients

A Monin, PS Baumann, A Griffa, L Xin, R Mekle, M Fournier, C Butticaz, M Klaey, JH Cabungcal, P Steullet, C Ferrari, M Cuenod, R Gruetter, JP Thiran, P Hagmann, P Conus, KQ Do

MOLECULAR PSYCHIATRY | NATURE PUBLISHING GROUP | Published : 2015

Abstract

Schizophrenia pathophysiology implies both abnormal redox control and dysconnectivity of the prefrontal cortex, partly related to oligodendrocyte and myelin impairments. As oligodendrocytes are highly vulnerable to altered redox state, we investigated the interplay between glutathione and myelin. In control subjects, multimodal brain imaging revealed a positive association between medial prefrontal glutathione levels and both white matter integrity and resting-state functional connectivity along the cingulum bundle. In early psychosis patients, only white matter integrity was correlated with glutathione levels. On the other side, in the prefrontal cortex of peripubertal mice with genetically..

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Grants

Awarded by Swiss National Science Foundation


Awarded by National Center of Competence in Research (NCCR) 'SYNAPSY-The Synaptic Bases of Mental Diseases'


Funding Acknowledgements

This work was supported by the Swiss National Science Foundation (Grant Nos. 310030_135736/1 to KQD and PS, 320030_122419 to PC and KQD and 130090 to PH) and the National Center of Competence in Research (NCCR) 'SYNAPSY-The Synaptic Bases of Mental Diseases' (Grant No. 51AU40_125759). We thank the Brazilian Swiss Joint Research Program (BSJRP), the 'Loterie Romande', Damm-Etienne Foundation, Avina Foundation and Alamaya Foundation. PH was financially supported by Leenaards Foundation. We are grateful for technical assistance to Helene Moser and Adeline Cottier. We also thank Dr Mehdi Gholam for advices on statistics, Dr Portia Vliet for the GCLC antibody and Dr Ibro Ambeskovic for advices on OPC culture and in vitro experiments. We extend thanks to Ying Chen for providing us with the GCLM-KO breeders. Most of all, we express our gratitude to all patients and healthy volunteers for their enduring participation.