Neurons and Microglia Differ in Depressed Brains
McGill researchers found altered gene activity in neurons and microglia from people with depression.
Researchers at McGill University and the Douglas Research Centre have identified two specific types of brain cells that show altered gene activity in people with depression. The findings, published in Nature Genetics, provide new insight into the cellular mechanisms associated with the condition.
The research team used post-mortem brain tissue from 100 individuals – 59 with depression and 41 without – donated to the Douglas-Bell Canada Brain Bank, 1 of the few brain banks worldwide that includes samples from people with psychiatric disorders.
“This is the first time we’ve been able to identify what specific brain cell types are affected in depression by mapping gene activity together with mechanisms that regulate the DNA code.”
Dr. Gustavo Turecki.
Focus on excitatory neurons and microglia
Using single-cell genomic techniques, the scientists examined gene expression and regulatory features in thousands of brain cells. This approach enabled them to identify differences in gene activity between the groups.
They found significant alterations in a type of excitatory neuron known to influence mood and stress regulation. Changes were also seen in a subtype of microglia, the brain’s immune cells involved in managing inflammation. Both cell types showed widespread gene expression differences in individuals with depression.
Microglia
Microglia are the primary immune cells of the central nervous system.
Single-cell genomic techniques
These methods allow researchers to study the genetic material of individual cells.
These findings highlight potential cellular disruptions in brain systems previously linked to mood regulation and immune responses.
Mapping regulatory changes at the single-cell level
The researchers not only examined gene expression but also looked at regulatory regions of DNA that control how genes are activated or silenced. This dual approach – combining transcriptomic and epigenomic data – allowed the team to link genetic regulation to specific cell types in the brain.
This level of resolution improves understanding of how gene activity is modulated in the context of mental illness, and may aid the development of more targeted therapeutic approaches.
“This research reinforces what neuroscience has been telling us for years. Depression isn’t just emotional, it reflects real, measurable changes in the brain.”
Dr. Gustavo Turecki.
Implications for future research
While the study does not establish direct causality or provide immediate therapeutic solutions, it offers a refined framework for understanding the cellular basis of depression. Future investigations will explore how these cellular alterations affect broader brain function and whether they can be modified through treatment.
Reference: Chawla A, Cakmakci D, Fiori LM, et al. Single-nucleus chromatin accessibility profiling identifies cell types and functional variants contributing to major depression. Nat Genet. 2025;57(8):1890-1904. doi: 10.1038/s41588-025-02249-4
This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source. Our press release publishing policy can be accessed here.
This content includes text that has been generated with the assistance of AI. Technology Networks' AI policy can be found here.
Add Technology Networks as a preferred Google source to see more of our trusted coverage.
