Varicose projection astrocytes: Conserved reactive cells in brain pathology
Astrocytes play essential roles in neuropathology. Human astrocytes exhibit unique properties, highlighting the importance of studying astrocytic responses in human models. Varicose projection astrocytes, previously considered exclusive to hominoids and a physiological type of astrocytes, were suggested to reflect pathological burden, albeit direct evidence linking them to neurological diseases has been lacking. Here, we demonstrate that varicose projection astrocytes also appear in other mammals and show, from four distinct human-based disease models, that varicose projection astrocytes are induced by neuroinflammation and characterized by distinctive subcellular features, indicating involvement in cellular stress responses, and their density is increased in aging and human neuropathology. Our findings establish varicose projection astrocytes as a reactive phenotype associated with neuropathology.
Authors
- Carlos Matute (ORCID: https://orcid.org/0000-0001-8672-711X)
- Marika Mearelli (ORCID: https://orcid.org/0009-0006-5168-3130)
- Saulius Ročka (ORCID: https://orcid.org/0000-0002-9715-641X)
- Ugnė Kuliešiūtė (ORCID: https://orcid.org/0000-0002-2097-4035)
- Luana Campos Soares (ORCID: https://orcid.org/0000-0001-9127-7061)
- Jean‐Marie Graïc (ORCID: https://orcid.org/0000-0002-1974-8356)
- Daniel C. Anthony (ORCID: https://orcid.org/0000-0003-1380-6655)
- Francesco Paolo Ulloa Severino (ORCID: https://orcid.org/0000-0003-3725-9713)
- Cinzia Centelleghe (ORCID: https://orcid.org/0000-0002-7577-2107)
- Carmen Falcone (ORCID: https://orcid.org/0000-0001-9892-1171)
- Fabio Cavaliere (ORCID: https://orcid.org/0000-0003-2003-522X)
- María‐Ángeles Arévalo (ORCID: https://orcid.org/0000-0002-4303-9576)
- Gediminas Lukšys
- Elena Christou
- Urtė Neniškytė (ORCID: https://orcid.org/0000-0001-7645-703X)
- Mootaz M. Salman (ORCID: https://orcid.org/0000-0002-5683-1706)
- Francesco Petrelli (ORCID: https://orcid.org/0000-0003-0696-7039)
- Paula Ramos‐Gonzalez
- Carmen Muñoz‐Ballester (ORCID: https://orcid.org/0000-0002-2298-7753)
- Alexei Verkhratsky (ORCID: https://orcid.org/0000-0003-2592-9898)
- Caterina Ciani (ORCID: https://orcid.org/0000-0003-2774-9321)
- Nunzio Iraci (ORCID: https://orcid.org/0000-0003-2146-9329)
- Giulio Pistorio
- Luca Mio
- Sari Elena Dötterer
- Simona Giancola
- Francesca Emma Mongelli
- Delaram Forouzeh
- Marta González Martín
- Marya Ayub (ORCID: https://orcid.org/0000-0002-1609-5281)
- Mandi E. Lichtenstein (ORCID: https://orcid.org/0009-0009-9245-9794)
- Kyle Hastings (ORCID: https://orcid.org/0009-0006-4637-873X)
- Anh Quynh Nguyen Do
Institutions
- University of Rome Tor Vergata (IT)
- Scuola Internazionale Superiore di Studi Avanzati (IT)
- University of Padua (IT)
- University of the Basque Country (ES)
- Vilnius University (LT)
- Universidad de Alcalá (ES)
- Instituto Cajal (ES)
- Instituto de Salud Carlos III (ES)
- University of Manchester (GB)
- Italian Institute of Technology (IT)
- University of Catania (IT)
- University of Oxford (GB)
- Biomedical Research Networking Center on Neurodegenerative Diseases (ES)
- Vilnius University of Applied Sciences (LT)
- Achucarro Basque Center for Neuroscience (ES)
- UK Dementia Research Institute (GB)
- Oxford BioMedica (United Kingdom) (GB)
- Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable (ES)
- Towson University (US)
- University of Maryland, Baltimore County (US)
- University of Lausanne (CH)
Publication Details
- Journal
- Science Advances
- Published
- 2026-07-17
- DOI
- https://doi.org/10.1126/sciadv.ady8204
- Primary Topic
- Systemic Sclerosis and Related Diseases
- Type
- article
- Field-Weighted Citation Impact
- 0.00