Scientists at Karolinska Institutet in Sweden and the University of North Carolina at Chapel Hill, USA, have identified cell types underlying a vast number of brain disorders in a new study published in Nature Genetics. Strikingly, they found that Parkinson’s disease was not only associated with cholinergic and monoaminergic neurons, but also with oligodendrocytes and enteric neurons, the latter supports that Parkinson’s disease could start in the gut. These findings offer a roadmap for the development of new therapies to target neurological and psychiatric disorders.
The nervous system is composed of hundreds of different cell types with very different functions. It is crucial to understand which cell types are affected in each disorder in order to understand the causes of the disorders and, ultimately, develop new treatments. In this study, the scientists have identified cell types underlying a large number of neurological and psychiatric conditions by testing whether genes specifically expressed in diverse cell types of the nervous system were more likely to be affected by genetic variants increasing risk for different brain disorders.
One of the disorders was Parkinson’s disease, a neurodegenerative disorder with motor symptoms resulting from a loss of dopaminergic neurons in a specific region of the brain.
“As expected, we found that dopaminergic neurons were associated with Parkinson’s disease. More surprisingly, we found that oligodendrocytes and enteric neurons also play an important role in the disorder,” says co-lead author Patrick Sullivan, MD, FRANZCP, Professor at the Department of Medical Epidemiology and Biostatistics at Karolinska Institutet and Yeargan Distinguished Professor in the Departments of Genetics and Psychiatry at the University of North Carolina.
By combining case-control differences in gene expression at different stages of Parkinson’s disease progression, the authors could show that oligodendrocytes were affected before the loss of dopaminergic neurons, suggesting that they play a key role in the early stages of the disease.
“These results suggest that oligodendrocyte could be an attractive target for therapeutic interventions as they appear to be affected before dopaminergic neurons,” says Julien Bryois, Postdoc at the Department of Medical Epidemiology and Biostatistics at Karolinska Institutet, one of the lead authors.
The association of Parkinson’s disease with neurons from the brain and neurons from the gut indicates that multiple regions of the nervous system are affected.
“The fact that the results from our analysis pointed us in a new direction where we could find de facto alterations in a cell type from patients shows that the analysis have practical implications”, says Jens Hjerling-Leffler, research group leader at the Department of Medical Biochemistry and Biophysics at Karolinska Institutet, one of the main authors.
University of North Carolina at Chapel Hill School of Medicine