Ectopic recruitment of neuroblasts in striatal myelin bundles and nucleus accumbens following AraC chemical lesion

Irini Thanou; Paraskevi N Koutsoudaki; Maria Margariti; Federico Luzzati; Sophia Havaki; Vassilis G Gorgoulis; Dimitra Thomaidou

doi:10.1016/j.stemcr.2025.102636

Ectopic recruitment of neuroblasts in striatal myelin bundles and nucleus accumbens following AraC chemical lesion

Stem Cell Reports. 2025 Sep 9;20(9):102636. doi: 10.1016/j.stemcr.2025.102636.

Authors

Irini Thanou¹, Paraskevi N Koutsoudaki², Maria Margariti¹, Federico Luzzati³, Sophia Havaki², Vassilis G Gorgoulis⁴, Dimitra Thomaidou⁵

Affiliations

¹ Neural Stem Cells and Neuroimaging Group, Department of Neurobiology, Hellenic Pasteur Institute, 11521 Athens, Greece.
² Molecular Carcinogenesis Group, Department of Histology and Embryology, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece.
³ Department of Life Sciences and Systems Biology (DBIOS), University of Turin, Turin 10123, Italy Neuroscience Institute Cavalieri Ottolenghi (NICO), 10043 Orbassano, Italy.
⁴ Molecular Carcinogenesis Group, Department of Histology and Embryology, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece; Biomedical Research Foundation, Academy of Athens, Athens, Greece; Ninewells Hospital and Medical School, University of Dundee, Dundee, UK; Faculty Institute for Cancer Sciences, Manchester Academic Health Sciences Centre, University of Manchester, Manchester, UK; Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK.
⁵ Neural Stem Cells and Neuroimaging Group, Department of Neurobiology, Hellenic Pasteur Institute, 11521 Athens, Greece. Electronic address: thomaidou@pasteur.gr.

Abstract

In the adult brain, neural stem cells (NSCs) constitutively generate new neurons in specific neurogenic domains. Recent research has unveiled reactive neurogenesis, whereby brain injury triggers NSC activation, enhancing their differentiation potential and guiding progeny to injured areas. Our study provides evidence of alternative migration pathways for newborn neurons in the mouse subcortical forebrain, revealed by administration of a chemotherapeutic agent. This allows a high number of newborn neurons to migrate long distances over an extended period. Notably, a subpopulation of neuroblasts diverts from the canonical SVZ-olfactory bulb (OB) rostral migratory stream toward the striatum (STR), with distinct localization along striatal myelin tracts and through nucleus accumbens (NAc) to the anterior commissure (AC). This neuroblast (NB) rerouting is accompanied by with oligodendrocyte lineage dysregulation and myelin deficits, suggesting a link between ectopic NB presence and observed myelin abnormalities.

Keywords: AraC; adult neurogenesis; ectopic migration; lesion-induced neurogenesis; myelin bundles; neuroblasts; striatum; subventricular zone.

MeSH terms

Animals
Cell Differentiation
Cell Movement / drug effects
Corpus Striatum* / cytology
Corpus Striatum* / metabolism
Corpus Striatum* / pathology
Mice
Myelin Sheath* / metabolism
Neural Stem Cells* / cytology
Neural Stem Cells* / drug effects
Neural Stem Cells* / metabolism
Neurogenesis
Neurons / cytology
Neurons / metabolism
Nucleus Accumbens* / cytology
Nucleus Accumbens* / drug effects
Nucleus Accumbens* / metabolism
Nucleus Accumbens* / pathology
Olfactory Bulb / metabolism
Oligodendroglia / cytology
Oligodendroglia / metabolism