Neuroscience and Beyond · Neuroscience and Beyond

The Brain’s Hidden Guardians: Microglia in Health and Disease | Dr. Verena Haage

·1 hr 5 min·4 clips

A large Alzheimer’s study traced microglia through homeostatic, interferon, inflammatory, and atrophic states.

1. Neuroscience and Beyond centers this episode on microglia, the brain’s resident immune cells, and their role in health and disease. 2. Host Svillen interviews Dr. Verena Hage, a guest scientist at Charité Berlin and former postdoc at Columbia University, and he connects her to the Kettenmann lab at the Max Delbrück Center. 3. The episode asks what microglia do, how researchers study them in mice and humans, and why leadership and mentorship also matter in scientific research. 4. Verena defines microglia as brain-resident macrophages and the first line of immune defense in the central nervous system. 5. She says microglia prune synaptic connections during development so the brain is wired correctly. 6. She explains that microglia maintain homeostasis in the brain and respond to stroke, glioma, ischemia, and neuroinflammation. 7. Svillen brings up the history of microglia, including Pio del Rigo Ortega, Santiago Ramón y Cajal, and the later revival of the field. 8. Verena says her research has shifted over 10 years from mouse microglia physiology and development to human microglia heterogeneity in aging and neurodegeneration. 9. She notes that single-cell RNA sequencing shows region-specific and temporally changing microglial states. 10. She says human and mouse microglia differ in gene expression and epigenetic regulation, which matters for therapeutic translation. 11. The conversation returns to the older “m1 and m2” framework and the fact that those states were defined in vitro with LPS. 12. Verena says single-cell RNA sequencing revealed a broader spectrum of microglia states and created a need for a common nomenclature. 13. She defines transcriptomics as an RNA-level snapshot and proteomics as a readout of what is happening at the functional protein level. 14. She says her lab mainly uses single-cell RNA sequencing and can isolate microglia from a brain region such as the hippocampus before sequencing each cell. 15. On human samples, she describes HMC3 cells, iPSC-derived microglia, cerebral organoids with implanted microglia, postmortem brain tissue in Hibernate A media, and fresh biopsy tissue from glioma and epilepsy cases. 16. She says fetal calf serum can alter microglial transcription and that fresh human microglia are difficult to transduce with viruses. 17. Verena says iPSC-derived microglia are promising for personalized medicine but do not fully recapitulate adult human microglia or the complexity of a whole organism. 18. She gives a concrete cost estimate of about $2,000 to $3,000 per single-cell RNA-seq sample and describes sample hashing with 10X to reduce costs. 19. The episode has an interview style that is conversational, technical, and occasionally corrective, with Svillen asking for definitions and examples throughout. 20. Listeners interested in glia biology, neurodegeneration, and experimental neuroscience will get the most from it, while people wanting a light general-audience chat may skip it.

As heard by us

A careful, concrete tour of microglia that stays grounded while it gets technical.

This episode tracks microglia, the brain's immune cells, from cleanup work into development and disease. Dr. Verena Hage handles the basics plainly, then adds the harder point: researchers still do not know when some states help or harm, or how much that turns on the state…

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A clear primer on brain microglia that also tracks the lab methods.

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