The MDPV Derivative α-PHP Regulates Cellular Differentiation and Triggers Apoptotic Cell Death and Ultrastructural Changes in Murine 3D Neurospheres
Fabrizio de Luca, Cinzia Brenna, M. Bassi, Sabrine Bilel, Adolfo Gregori, C. Locatelli, Luca M. Neri, Raffaella Adami, Daniele Bottai, Matteo Marti, Elisa Roda
Molecules July 13, 2026 DOI: 10.3390/molecules31142453 (opens in new tab) via OpenAlex
Summary
AI-generated from the abstractThe synthetic cathinone αPHP, a derivative of MDPV, induces dose-dependent neurotoxic effects in mouse neural stem/progenitor cells grown in 2D cultures and 3D neurospheres. Exposure to concentrations from 50 to 2000 μM alters cell morphology, disrupts neuronal and glial differentiation, activates apoptotic cell death pathways, and causes ultrastructural changes. These findings suggest that αPHP is neurotoxic and neuromodulatory, contributing to understanding the mechanisms behind psychiatric and neurological outcomes from synthetic cathinones.
Study at a glance
| Characteristics | In vitro study Peer reviewed |
|---|---|
| Population | Murine 2D neural stem/progenitor cell cultures and 3D neurospheres |
| Intervention | αPHP |
| Dose | 50–2000 μM |
| Keywords | Neurosphere Apoptosis Programmed cell death Neural stem cell Ultrastructure |
| Key finding | αPHP induced a dose-dependent neurotoxic and neuromodulatory effect in murine neural stem/progenitor cell cultures and neurospheres, affecting differentiation, activating apoptosis, and altering morphology and ultrastructure. |
Abstract
Cumulative reports of psychiatric and neurological outcomes due to synthetic cathinones continue to raise public concern. However, the understanding of the neurotoxic mechanism of action is still poorly understood, particularly for the under-explored αPHP, one of the main MDPV derivatives. In particular, the effects of this synthetic drug on neural stem/progenitor cell cultures are still unknown. Therefore, in the proposed in vitro study, the effects of increasing αPHP concentrations (50–2000 μM) on cell morphology, neuronal/glial differentiation, cell death pathways, and ultrastructure have been evaluated after exposure in murine 2D NSPCs and 3D neurospheres using complementary techniques, i.e., phase contrast microscopy, immunocytochemistry, confocal microscopy, and transmission electron microscopy. We observed that αPHP was able to induce a dose-dependent neurotoxic and neuromodulatory effect in murine 2D NSPC cultures and a 3D neurosphere model, affecting neuronal/glial differentiation, activating the apoptotic pathway, and inducing morphological and ultrastructural changes. The present study could pave the way for a broadened knowledge of synthetic cathinone (SCs) toxicology, needed to establish the right treatment for novel psychoactive substance (NPS) exposure and the possible consequences for public health.