Correa da Silva & Huitinga (2025)
- Authors: Felipe Correa da Silva, Inge Huitinga
- Institutes: Netherlands Institute for Neuroscience (NIN-KNAW), Amsterdam, Netherlands, University of Amsterdam, Amsterdam, Netherlands, Netherlands Brain Bank (NBB), Amsterdam, Netherlands
- Publisher: NMCB / ZonMw
- Link: DOI
Summary
This landmark autopsy study represents the first systematic, high-resolution analysis of brain tissue from a dedicated ME/CFS cohort. By identifying specific neuro-endocrine changes in the hypothalamus, the research provides a potential biological basis for the HPA-axis dysfunction and autonomic symptoms characteristic of the disease. This work shifts the focus from broad neuroinflammation to specific cellular and molecular changes in regulatory brain regions.
What was researched?
This research involved a comprehensive post-mortem analysis of brain tissue from the first ten donors in the Dutch ME/CFS Brain Bank to identify structural and molecular abnormalities.
Why was it researched?
The study aimed to investigate the ‘brain disease’ hypothesis of ME/CFS by looking for physical evidence of neuro-endocrine disruption, neuroinflammation, and mitochondrial dysfunction that cannot be observed via standard clinical imaging.
How was it researched?
Researchers performed detailed histological and molecular examinations on tissue from ten autopsied ME/CFS patients, focusing on the hypothalamus, microglial activation, and mitochondrial protein expression. The study also utilized advanced single-cell transcriptomics across multiple brain regions to map gene expression changes in specific cell types.
What has been found?
The analysis revealed significant changes in the hypothalamus, specifically involving neurons producing corticotropin-releasing hormone (CRH) and vasopressin. While widespread chronic neuroinflammation was not observed, the study found evidence of altered microglial states and mitochondrial signatures. Single-cell sequencing identified unique molecular patterns in glia and neurons that distinguish ME/CFS brain tissue from controls.
Discussion
A major strength of this study is the high-quality, short-post-mortem-interval tissue provided by the specialized Dutch Brain Bank. Limitations include the small initial sample size of ten cases and the inherent complexity of interpreting post-mortem changes in long-term chronic illness.
Conclusion & Future Work
The findings suggest that ME/CFS involves specific neurobiological alterations in the HPA-axis regulation center rather than generalized brain inflammation. Future work will expand the cohort to validate these findings and explore their relationship with clinical symptom severity.