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The MDPV Derivative α-PHP Regulates Cellular Differentiation and Triggers Apoptotic Cell Death and Ultrastructural
Fabrizio De Luca1, Cinzia Brenna2,3, Marta Bassi4
1Department of Biology and Biotechnology "L. Spallanzani", University of Pavia, 27100 Pavia, Italy.
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.
Insights
Alpha-PHP, a synthetic cathinone, causes dose-dependent neurotoxicity in neural stem cells. This study reveals its impact on cell differentiation, death pathways, and structure, impacting public health.
Area of Science:
- Neuroscience
- Toxicology
- Cell Biology
Background:
- Synthetic cathinones (SCs), including alpha-PHP, are linked to severe psychiatric and neurological outcomes.
- The neurotoxic mechanisms of SCs, especially alpha-PHP, remain poorly understood.
- The impact of alpha-PHP on neural stem/progenitor cells (NSPCs) is largely unknown.
Purpose of the Study:
- To investigate the in vitro neurotoxic and neuromodulatory effects of alpha-PHP on murine 2D NSPCs and 3D neurospheres.
- To evaluate dose-dependent effects of alpha-PHP on cell morphology, neuronal/glial differentiation, cell death, and ultrastructure.
Main Methods:
- Murine 2D NSPCs and 3D neurospheres were exposed to increasing concentrations of alpha-PHP (50-2000 μM).
- Techniques included phase contrast microscopy, immunocytochemistry, confocal microscopy, and transmission electron microscopy.
- Evaluated parameters were cell morphology, differentiation, apoptosis, and ultrastructural changes.
Main Results:
- Alpha-PHP induced dose-dependent neurotoxic and neuromodulatory effects in both 2D and 3D NSPC models.
- Observed effects included altered neuronal/glial differentiation and activation of apoptotic pathways.
- Significant morphological and ultrastructural changes were induced by alpha-PHP exposure.
Conclusions:
- Alpha-PHP exhibits significant neurotoxicity and neuromodulatory actions on developing neural cells.
- Findings highlight the potential risks of novel psychoactive substance (NPS) exposure for public health.
- This research contributes to understanding SC toxicology for improved clinical treatment strategies.
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