Varicose projection astrocytes: Conserved reactive cells in brain pathology

Science Advances 2026 Open access

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Authors: Caterina Ciani, Giulio Pistorio, Simona Giancola, Marika Mearelli, Francesca Emma Mongelli, Delaram Forouzeh, Luana Campos Soares, Marta González Martín, Mandi E. Lichtenstein, Luca Mio, Elena Christou, Kyle Hastings
+21 more Anh Quynh Nguyen Do, Paula Ramos‐Gonzalez, Carlos Matute, Ugnė Kuliešiūtė, Sari Elena Dötterer, Gediminas Lukšys, Saulius Ročka, Urtė Neniškytė, Daniel C. Anthony, Marya Ayub, Cinzia Centelleghe, María‐Ángeles Arévalo, Jean‐Marie Graïc, Francesco Petrelli, Alexei Verkhratsky, Nunzio Iraci, Fabio Cavaliere, Carmen Muñoz‐Ballester, Mootaz M. Salman, Francesco Paolo Ulloa Severino, Carmen Falcone
DOI: 10.1126/sciadv.ady8204
Cited by: 3
References: 54

Abstract

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.

Fields of Study & Subjects

Systemic Sclerosis and Related Diseases Multiple Sclerosis Research Studies Neuroinflammation and Neurodegeneration Mechanisms

Publication details

Journal / source
Science Advances
Publisher
American Association for the Advancement of Science (AAAS)
Volume
12
Issue
29
Pages
eady8204–eady8204
Publication date
17 July 2026
Language
EN