Neural precursor cells tune striatal connectivity through the release of IGFBPL1
Erica Butti, Stefano Cattaneo, Marco Bacigaluppi, Marco Cambiaghi, Giulia Maria Scotti, Elena Brambilla, Francesca Ruffini, Giacomo Sferruzza, Maddalena Ripamonti, Fabio Simeoni, Laura Cacciaguerra, Aurora Zanghì, Angelo Quattrini, Riccardo Fesce, Paola Panina‐Bordignon, Francesca Giannese, Davide Cittaro, Tanja Kuhlmann, Patrizia D’Adamo, Maria A. Rocca, Stefano Taverna, Gianvito Martino
Abstract
The adult brain retains over life endogenous neural stem/precursor cells (eNPCs) within the subventricular zone (SVZ). Whether or not these cells exert physiological functions is still unclear. In the present work, we provide evidence that SVZ-eNPCs tune structural, electrophysiological, and behavioural aspects of striatal function via secretion of insulin-like growth factor binding protein-like 1 (IGFBPL1). In mice, selective ablation of SVZ-eNPCs or selective abrogation of IGFBPL1 determined an impairment of striatal medium spiny neuron morphology, a higher failure rate in GABAergic transmission mediated by fast-spiking interneurons, and striatum-related behavioural dysfunctions. We also found IGFBPL1 expression in the human SVZ, foetal and induced-pluripotent stem cell-derived NPCs. Finally, we found a significant correlation between SVZ damage, reduction of striatum volume, and impairment of information processing speed in neurological patients. Our results highlight the physiological role of adult SVZ-eNPCs in supporting cognitive functions by regulating striatal neuronal activity.