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Evaluating the potential of methylphenidate and amphetamine acute exposure to promote neurite outgrowth and synaptogenesis in differentiated SH-SY5Y neuronal cells.
* , , , *
1  Associate Laboratory i4HB - Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal
2  UCIBIO - Applied Molecular Biosciences Unit, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, 4050‐313 Porto, Portugal
3  FP-I3ID, Faculdade de Ciências da Saúde, Universidade Fernando Pessoa, Porto, Portugal
Academic Editor: Alfredo Berzal-Herranz

Published: 01 November 2022 by MDPI in 8th International Electronic Conference on Medicinal Chemistry session General (registering DOI)

Methylphenidate (MPH) and amphetamine (AMPH) increase monoamine levels in the synaptic cleaft, due to their properties and similarities to monoamine neurotransmitters. Stroke and traumatic brain injury, common neurological diseases, affect millions of people every year. Their treatment mainly focuses on the focal point and symptoms, lacking on the curative measures and neural repair. In in vitro and in vivo models, MPH and AMPH showed to promote neuronal recovery following injury through neurite outgrowth.

Thus, this study evaluated the neurite outgrowth and synaptogenesis promoted by clinical relevant concentrations of AMPH and MPH in a neuronal human model, differentiated SH-SY5Y. The cells were exposed to 0.001, 0.01, 0.1, 1 and 10µM of drugs for 24h. Our results reveled that after 24h, AMPH and MPH were not cytotoxic to differentiated SH-SY5Y, by either the MTT reduction or the NR uptake assays. Also, the concentrations of 0.1 and 0.01µM did not affect the expression of synaptophysin, PSD95 and GAP43 evaluated by Western blotting. Moreover, neurite outgrowth was evaluated in microphotographs resourcing to the NeuronJ software and no enhancement of neurite outgrowth in differentiated SH-SY5Y cells was promoted by AMPH or MPH at the concentrations of 0.1 and 0.01µM.

As far as we know, this is the first study evaluating the effect of clinical relevant concentrations of MPH and AMPH in a paradigm of acute exposure to neuronal SH-SY5Y cells, being the starting point to our strategy to understand the possible effects of MPH and AMPH on the improvement of neural network.

Keywords: Methylphenidate; Amphetamine; SH-SY5Y; Stroke; Traumatic Brain Injury; Neurite Outgrowth; Synaptogenesis.