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Methylphenidate alters Akt‐mTOR signaling in rat pheochromocytoma cells
Author(s) -
Schmitz Felipe,
Chao Moses V.,
Wyse Angela T.S.
Publication year - 2019
Publication title -
international journal of developmental neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.761
H-Index - 88
eISSN - 1873-474X
pISSN - 0736-5748
DOI - 10.1016/j.ijdevneu.2018.12.004
Subject(s) - pi3k/akt/mtor pathway , protein kinase b , p70 s6 kinase 1 , creb , methylphenidate , gsk 3 , protein kinase a , phosphorylation , pharmacology , chemistry , medicine , endocrinology , biology , microbiology and biotechnology , signal transduction , psychiatry , biochemistry , attention deficit hyperactivity disorder , transcription factor , gene
The exponential increase in methylphenidate (MPH) prescriptions in recent years has worried researchers about its misuse among individuals who do not meet the full diagnostic criteria for attention‐deficit/hyperactivity disorder (ADHD) such as young children and students in search of cognitive improvement or for recreational reasons. The action of MPH is based mainly on inhibition of dopamine transporter, but the complete cellular effects are still unknown. Based upon prior studies, we attempted to determine whether the treatment with MPH (1μM) influences protein kinase B‐mammalian target of rapamycin complex 1 signaling pathways (Akt‐mTOR), including translation repressor protein (4E‐BP1) and mitogen activated protein kinase (S6K), in rat pheochromocytoma cells (PC12), a well characterized cellular model, in a long or short term. MPH effects on the Akt substrates [cAMP response element‐binding protein (CREB), forkhead box protein O1 (FoxO1), and glycogen synthase kinase 3 beta (GSK‐3β)] were also evaluated. Whereas short term MPH treatment decreased the pAkt/Akt, pmTOR/mTOR and pS6K/S6K ratios, as well as pFoxO1 immunocontent in PC12 cells, long term treatment increased pAkt/Akt, pmTOR/mTOR and pGSK‐3β/GSK‐3β ratio. Phosphorylation levels of 4E‐BP1 were decreased at 15 and 30 min and increased at 1 and 6 h by MPH. pCREB/CREB ratio was decreased. This study shows that the Akt‐mTOR pathway, as well as other important Akt substrates which have been described as important regulators of protein synthesis, as well as being implicated in cellular survival, synaptic plasticity and memory consolidation, was affected by MPH in PC12 cells, representing an important step in exploring the MPH effects.