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 Assunta Rocca, Stefano Taverna and Gianvito Martino ()
Additional contact information
Erica Butti: Institute of Experimental Neurology (INSPE), IRCCS San Raffaele Hospital
Stefano Cattaneo: Institute of Experimental Neurology (INSPE), IRCCS San Raffaele Hospital
Marco Bacigaluppi: Institute of Experimental Neurology (INSPE), IRCCS San Raffaele Hospital
Marco Cambiaghi: University of Verona
Giulia Maria Scotti: IRCCS San Raffaele Hospital
Elena Brambilla: Institute of Experimental Neurology (INSPE), IRCCS San Raffaele Hospital
Francesca Ruffini: Institute of Experimental Neurology (INSPE), IRCCS San Raffaele Hospital
Giacomo Sferruzza: Institute of Experimental Neurology (INSPE), IRCCS San Raffaele Hospital
Maddalena Ripamonti: Institute of Experimental Neurology (INSPE), IRCCS San Raffaele Hospital
Fabio Simeoni: IRCCS San Raffaele Hospital
Laura Cacciaguerra: Institute of Experimental Neurology (INSPE), Division of Neuroscience, IRCCS San Raffaele Hospital
Aurora Zanghì: Institute of Experimental Neurology (INSPE), Division of Neuroscience, IRCCS San Raffaele Hospital
Angelo Quattrini: Division of Neuroscience, IRCCS San Raffaele Hospital
Riccardo Fesce: Humanitas University, Pieve Emanuele
Paola Panina-Bordignon: Institute of Experimental Neurology (INSPE), IRCCS San Raffaele Hospital
Francesca Giannese: IRCCS San Raffaele Hospital
Davide Cittaro: IRCCS San Raffaele Hospital
Tanja Kuhlmann: University Hospital Muster
Patrizia D’Adamo: Division of Neuroscience, IRCCS San Raffaele Hospital
Maria Assunta Rocca: Vita-Salute San Raffaele University
Stefano Taverna: Institute of Experimental Neurology (INSPE), IRCCS San Raffaele Hospital
Gianvito Martino: Institute of Experimental Neurology (INSPE), IRCCS San Raffaele Hospital

Nature Communications, 2022, vol. 13, issue 1, 1-23

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-35341-y

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