The Designer Drug αPHP Affected Cell Proliferation and Triggered Deathly Mechanisms in Murine Neural Stem/Progenitor Cells
Elisa Roda,
Fabrizio De Luca,
Erica Cecilia Priori,
Daniela Ratto,
Silvana Pinelli,
Emilia Corradini,
Paola Mozzoni,
Diana Poli,
Giuliano Mazzini,
Maria Grazia Bottone,
Anna Maria Gatti,
Matteo Marti,
Carlo Alessandro Locatelli,
Paola Rossi,
Daniele Bottai
Affiliations
Elisa Roda
Laboratory of Clinical & Experimental Toxicology, Pavia Poison Centre, National Toxicology Information Centre, Toxicology Unit, Istituti Clinici Scientifici Maugeri IRCCS, 27100 Pavia, Italy
Fabrizio De Luca
Department of Biology and Biotechnology “L. Spallanzani”, University of Pavia, 27100 Pavia, Italy
Erica Cecilia Priori
Department of Biology and Biotechnology “L. Spallanzani”, University of Pavia, 27100 Pavia, Italy
Daniela Ratto
Department of Biology and Biotechnology “L. Spallanzani”, University of Pavia, 27100 Pavia, Italy
Silvana Pinelli
Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy
Emilia Corradini
Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy
Paola Mozzoni
Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy
Diana Poli
INAIL Research, Department of Occupational and Environmental Medicine, Epidemiology and Hygiene, Via Fontana Candida, 1, 00078 Monte Porzio Catone, Italy
Giuliano Mazzini
Department of Biology and Biotechnology “L. Spallanzani”, University of Pavia, 27100 Pavia, Italy
Maria Grazia Bottone
Department of Biology and Biotechnology “L. Spallanzani”, University of Pavia, 27100 Pavia, Italy
Anna Maria Gatti
Laboratory of Clinical & Experimental Toxicology, Pavia Poison Centre, National Toxicology Information Centre, Toxicology Unit, Istituti Clinici Scientifici Maugeri IRCCS, 27100 Pavia, Italy
Matteo Marti
Department of Translational Medicine, Section of Legal Medicine, LTTA Center and University Center of Gender Medicine, University of Ferrara, 44121 Ferrara, Italy
Carlo Alessandro Locatelli
Laboratory of Clinical & Experimental Toxicology, Pavia Poison Centre, National Toxicology Information Centre, Toxicology Unit, Istituti Clinici Scientifici Maugeri IRCCS, 27100 Pavia, Italy
Paola Rossi
Department of Biology and Biotechnology “L. Spallanzani”, University of Pavia, 27100 Pavia, Italy
Daniele Bottai
Department of Pharmaceutical Sciences, Section of Pharmacology and Biosciences, University of Milan, Via Balzaretti 9, 20133 Milan, Italy
Increasing reports of neurological and psychiatric outcomes due to psychostimulant synthetic cathinones (SCs) have recently raised public concern. However, the understanding of neurotoxic mechanisms is still lacking, particularly for the under-investigated αPHP, one of the major MDPV derivatives. In particular, its effects on neural stem/progenitor cell cultures (NSPCs) are still unexplored. Therefore, in the current in vitro study, the effects of increasing αPHP concentrations (25–2000 μM), on cell viability/proliferation, morphology/ultrastructure, genotoxicity and cell death pathways, have been evaluated after exposure in murine NSPCs, using a battery of complementary techniques, i.e., MTT and clonogenic assay, flow cytometry, immunocytochemistry, TEM, and patch clamp. We revealed that αPHP was able to induce a dose-dependent significant decrease of the viability, proliferation and clonal capability of the NSPCs, paralleled by the resting membrane potential depolarization and apoptotic/autophagic/necroptotic pathway activation. Moreover, ultrastructural alterations were clearly observed. Overall, our current findings demonstrate that αPHP, damaging NSPCs and the morpho-functional fundamental units of adult neurogenic niches may affect neurogenesis, possibly triggering long-lasting, irreversible CNS damage. The present investigation could pave the way for a broadened understanding of SCs toxicology, needed to establish an appropriate treatment for NPS and the potential consequences for public health.
