A preliminary study on methylphenidate-regulated gene expression in lymphoblastoid cells of ADHD patients

Schwarz, Ricarda; Reif, Andreas; Scholz, Claus‐Jürgen; Weissflog, L.; Schmidt, Brigitte; Lesch, Klaus‐Peter; Jacob, Christian; Reichert, Susanne; Heupel, Julia; Volkert, Julia; Kopf, Juliane; Hilscher, Max; Weber, Heike; Kittel‐Schneider, Sarah

doi:10.3109/15622975.2014.948064

Cited by 12 publications

(10 citation statements)

References 58 publications

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“…We re-analyzed three available gene expression profile data sets extracted from the GEO database, from experiments studying MPH treatment effects in mouse substantia nigra 27 , in rat striatum and frontal cortex 28 , and in immortalized human lymphocytes of controls and adult ADHD patients 29 , in which in the last study cell lines were acutely treated with ca. 111 μM MPH.…”

Section: Resultsmentioning

confidence: 99%

“…A search of data sets under GEO was conducted for gene expression profiling results after MPH treatment conducted in mammals with the keyword ‘methylphenidate’ and limiting the search to the ‘expression profiling by array’ study type. Three data sets could be found (excluding one dealing with autism spectrum disorder) using these terms: (1) MPH effect on mouse substantia nigra 27 —GSE33619, (2) Psychostimulant (MPH, amphetamine and methamphetamine) effects on rat striatum and prefrontal cortex 28 —GSE33619, and (3) MPH effects on human lymphoblastoids 29 —GSE52889. Following this, each of the data sets were uploaded onto the Pathway Studio software (Elsevier; v. 11.4.08) to run the gene expression profiling and statistics correcting for multiple testing with Benjamin–Hochberg (FDR).…”

Section: Methodsmentioning

confidence: 99%

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Methylphenidate enhances neuronal differentiation and reduces proliferation concomitant to activation of Wnt signal transduction pathways

2018

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Methylphenidate (Ritalin) is the most commonly prescribed drug in the treatment of attention-deficit hyperactivity disorder. It is suggested that in vivo, methylphenidate treatment supports cortical maturation, however, the molecular and cellular mechanisms are not well understood. This study aimed to explore the potential effect of methylphenidate on cell proliferation and maturation in various cellular models, hypothesizing its interaction with the Wnt-signaling. The termination of cell proliferation concomitant to neuronal maturation following methylphenidate treatment was observed in all of the cell-models tested: murine neural stem-, rat PC12- and the human SH-SY5Y-cells. Inhibition of Wnt-signaling in SH-SY5Y cells with Dkk1 30 min before methylphenidate treatment suppressed neuronal differentiation but enhanced proliferation. The possible involvement of the dopamine-transporter in cell differentiation was discounted following the observation of opposing results after GBR-12909 treatment. Moreover, Wnt-activation via methylphenidate was confirmed in Wnt-luciferase-reporter assay. These findings reveal a new mechanism of action of methylphenidate that might explain long-term effects.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Methylphenidate enhances neuronal differentiation and reduces proliferation concomitant to activation of Wnt signal transduction pathways

2018

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“…These studies should integrate hypothesis-driven and hypothesis-free gene expression experiments, under both basal and drug-treatment conditions, to assess possible modes of drug action. A number of studies have already addressed the effects of psychostimulants in cell culture, however these studies relied on animal cell culture models, non-neuronal human cell models and/ or transfection systems for overexpression of the dopamine (DAT) or norepinephrine transporter (Grünblatt et al 2013;Schwarz et al 2014). For example, in a murine stem cell model, it was shown that methylphenidate treatment in vitro could enhance neuronal differentiation (Bartl et al 2013).…”

Section: Attention-deficit/hyperactivity Disordermentioning

confidence: 99%

Mental health dished up—the use of iPSC models in neuropsychiatric research

et al. 2020

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Genetic and molecular mechanisms that play a causal role in mental illnesses are challenging to elucidate, particularly as there is a lack of relevant in vitro and in vivo models. However, the advent of induced pluripotent stem cell (iPSC) technology has provided researchers with a novel toolbox. We conducted a systematic review using the PRISMA statement. A PubMed and Web of Science online search was performed (studies published between 2006–2020) using the following search strategy: hiPSC OR iPSC OR iPS OR stem cells AND schizophrenia disorder OR personality disorder OR antisocial personality disorder OR psychopathy OR bipolar disorder OR major depressive disorder OR obsessive compulsive disorder OR anxiety disorder OR substance use disorder OR alcohol use disorder OR nicotine use disorder OR opioid use disorder OR eating disorder OR anorexia nervosa OR attention-deficit/hyperactivity disorder OR gaming disorder. Using the above search criteria, a total of 3515 studies were found. After screening, a final total of 56 studies were deemed eligible for inclusion in our study. Using iPSC technology, psychiatric disease can be studied in the context of a patient’s own unique genetic background. This has allowed great strides to be made into uncovering the etiology of psychiatric disease, as well as providing a unique paradigm for drug testing. However, there is a lack of data for certain psychiatric disorders and several limitations to present iPSC-based studies, leading us to discuss how this field may progress in the next years to increase its utility in the battle to understand psychiatric disease.

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“…Mechanisms modulating gene expression such as those proposed by Schwarz et al [22] following chronic MPH treatment might underlie the long-term metaplastic changes reported here.…”

mentioning

confidence: 75%

Methylphenidate has long-lasting metaplastic effects in the prefrontal cortex of adolescent rats

Burgos

Cofré²,

Hernández³

et al. 2015

Behavioural Brain Research

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A preliminary study on methylphenidate-regulated gene expression in lymphoblastoid cells of ADHD patients

Cited by 12 publications

References 58 publications

Methylphenidate enhances neuronal differentiation and reduces proliferation concomitant to activation of Wnt signal transduction pathways

Methylphenidate enhances neuronal differentiation and reduces proliferation concomitant to activation of Wnt signal transduction pathways

Mental health dished up—the use of iPSC models in neuropsychiatric research

Methylphenidate has long-lasting metaplastic effects in the prefrontal cortex of adolescent rats

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