Homeostasis of dopamine,a classical neurotransmitter,is a key indicator of neuronal health.Dysfunction in the regulation of dopamine is implicated in a long list of neurological disorders,including addiction,depressio...Homeostasis of dopamine,a classical neurotransmitter,is a key indicator of neuronal health.Dysfunction in the regulation of dopamine is implicated in a long list of neurological disorders,including addiction,depression,and neurodegeneration.The existing methods used to evaluate dopamine homeostasis in vitro are inconvenient and do not allow for continuous non-destructive measurement.In response to this challenge,we introduce an integrated microfluidic system that combines dopaminergic cell culture and differentiation with electroanalytical measurements of extracellular dopamine in real-time at any point during an assay.We used the system to examine the behavior of differentiated SH-SY5Y cells upon exposure to four dopamine transporter ant/agonists(cocaine,ketamine,epigallocatechin gallate,and amphetamine)and study their pharmacokinetics.The IC_(50)values of cocaine,ketamine,and epigallocatechin gallate were determined to be(average±standard deviation)3.7±1.1μM,51.4±17.9μM,and 2.6±0.8μM,respectively.Furthermore,we used the new system to study amphetamine-mediated dopamine release to probe the related phenomena of dopamine transporter-mediated reverse-transport and dopamine release from vesicles.We propose that this platform,which is the first platform to simultaneously evaluate uptake and release,could be useful to screen for drugs and other agents that target dopaminergic neurons and the function of the dopamine transporter.More broadly,this platform should be adaptable for any application that could benefit from high-temporal resolution electroanalysis combined with multi-day cell culture using small numbers of cells.展开更多
Correction to:Microsystems&Nanoengineering(2019)5:10 https://doi.org/10.1038/s41378-019-0049-2 published online:11 March 2019 The legend in Fig.4a in the previously published version of this article contained erro...Correction to:Microsystems&Nanoengineering(2019)5:10 https://doi.org/10.1038/s41378-019-0049-2 published online:11 March 2019 The legend in Fig.4a in the previously published version of this article contained erroneous units.The correct units are given in the caption–that is,1μM(black),500 nM(red),100 nM(blue),50 nM(cyan),10 nM(pink),and 0 nM(1×PBS solution,brown).展开更多
基金which is supported by the Canada First Research Excellence Fund(CFREF)for funding。
文摘Homeostasis of dopamine,a classical neurotransmitter,is a key indicator of neuronal health.Dysfunction in the regulation of dopamine is implicated in a long list of neurological disorders,including addiction,depression,and neurodegeneration.The existing methods used to evaluate dopamine homeostasis in vitro are inconvenient and do not allow for continuous non-destructive measurement.In response to this challenge,we introduce an integrated microfluidic system that combines dopaminergic cell culture and differentiation with electroanalytical measurements of extracellular dopamine in real-time at any point during an assay.We used the system to examine the behavior of differentiated SH-SY5Y cells upon exposure to four dopamine transporter ant/agonists(cocaine,ketamine,epigallocatechin gallate,and amphetamine)and study their pharmacokinetics.The IC_(50)values of cocaine,ketamine,and epigallocatechin gallate were determined to be(average±standard deviation)3.7±1.1μM,51.4±17.9μM,and 2.6±0.8μM,respectively.Furthermore,we used the new system to study amphetamine-mediated dopamine release to probe the related phenomena of dopamine transporter-mediated reverse-transport and dopamine release from vesicles.We propose that this platform,which is the first platform to simultaneously evaluate uptake and release,could be useful to screen for drugs and other agents that target dopaminergic neurons and the function of the dopamine transporter.More broadly,this platform should be adaptable for any application that could benefit from high-temporal resolution electroanalysis combined with multi-day cell culture using small numbers of cells.
文摘Correction to:Microsystems&Nanoengineering(2019)5:10 https://doi.org/10.1038/s41378-019-0049-2 published online:11 March 2019 The legend in Fig.4a in the previously published version of this article contained erroneous units.The correct units are given in the caption–that is,1μM(black),500 nM(red),100 nM(blue),50 nM(cyan),10 nM(pink),and 0 nM(1×PBS solution,brown).
