image:

Kerstin Lenk, Institute of Neural Engineering, TU Graz.

Credit: Fotogenia

Women are diagnosed with severe depression about twice as often as men, though the underlying causes remain unclear. One area under investigation is whether the blood-brain barrier functions differently between sexes. This critical barrier, made up of astrocytes (branched brain cells) and endothelial cells (which form the inner lining of blood vessels), defends the brain from harmful substances. When it becomes compromised, various brain disorders may result. Kerstin Lenk of TU Graz, working alongside researchers from the University of Regensburg, is exploring how the blood-brain barrier might behave differently during depression—and whether sex plays a significant role in this. Their joint study, titled “Leaky blood-brain barrier in major depressive disorder,” is supported by the Austrian Science Fund and the German Research Foundation. Particular attention is paid to how these mechanisms differ in men and women.

At the University of Regensburg, cultured cells are used to study the interaction between astrocytes and endothelial cells in both healthy and depressed brain models. Through a combination of biochemical and pharmacogenetic tools, the team identifies how specific cell processes may influence depression. Kerstin Lenk and her colleagues then convert this data into virtual models—digital replicas of the blood-brain barrier and the cells involved. These simulations help them examine how chemical signals move between cells under various conditions. Additionally, artificial intelligence is being employed to detect sex-based patterns in the data.

“Our goal is to deepen the understanding of how depressive disorders emerge, and why their progression might differ between women and men,” says Kerstin Lenk. “This could pave the way for more personalized and effective treatments.”

Growing Focus on Biological Sex in Brain Research

The collaborative efforts in Graz and Regensburg are part of a broader trend in neuroscience that emphasizes the significance of biological sex in research. Kerstin Lenk was one of the co-authors of a recent review article published in Nature Reviews Bioengineering. The piece, titled “Modelling sex differences of neurological disorders in vitro,” discusses the growing recognition of sex-specific biology in understanding brain diseases. Laboratory tools like stem cell models, 3D mini-brains, and organ-on-a-chip systems are increasingly used to reflect these differences in research, enhancing how findings can be translated into real-world medical applications. These physical models are also being paired with emerging technologies such as computer simulations and AI to offer more comprehensive insights.

Journal

Nature Reviews Bioengineering

DOI

10.1038/s44222-025-00355-w

Method of Research

Experimental study

Subject of Research

Cells

Article Title

Modelling sex differences of neurological disorders in vitro

Article Publication Date

13-Oct-2025