Centre for Clinical Brain Sciences

New publication: a link between glial cell disruption and major mental illness

Sep 2019: CCBS researchers have published findings suggesting a link between changes in oligodendroglia and major mental illness.

The team of researchers, led by Dr Navneet Vasistha, Dr Mandy Johnstone and Professor Siddharthan Chandran, took stem cells from individuals in a family, some of whom were affected with major mental illness and some of whom were not. The affected members of this family carry a chromosomal translocation, a genetic abnormality that puts them at higher risk of mental illness.

Using established protocols to generate oligodendroglia - the cells that make myelin - they found that cells generated from affected family members grew less well and were severely stunted in comparison with their healthy counterparts. In addition, they also found the levels of several genes related to oligodendroglia development to be altered.

To test the effect of these cellular changes on the brain, the team grafted these cells into mice deficient for myelin. As had been suggested by the earlier experiments, grafted oligodendroglia from affected individuals were deficient in myelin compared with those from healthy individuals.

Interestingly, earlier brain MRI scans of individuals from this same family had shown that affected members had disrupted connections between brain regions, suggestive of faulty myelin.

Combining stem cell technologies with brain imaging, genomics and transcriptomics allowed the team to link dysfunction at a cellular and molecular level with genetic changes and disease status. This is crucial to gaining a greater understanding of mental illness and the pursuit of more effective disease-modifying treatments.

Related links

Read the publication in Molecular Psychiatry:  Familial t(1;11) translocation is associated with disruption of white matter structural integrity and oligodendrocyte–myelin dysfunction by Vasistha et al. doi.org/10.1038/s41380-019-0505-2

Stem cell biology & regenerative neurology research at the Centre for Clinical Brain Sciences

Professor Siddharthan Chandran's profile