Methadone interrupts neural growth and function in human cortical organoids

Yao H, Wu W, Cerf I, Zhao HW, Wang J, Negraes PD, Muotri AR, Haddad GG.

Stem Cell Research, 2020


The authors generated human cortical organoids from induced pluripotent stem cells and showed that methadone halted the growth and lead to disintegration in the cortical organoids.  Furthermore, methadone suppressed the neural network activity by weakening the synaptic transmission with the human cortical organoid.

Methadone is a known opioid that affects human fetal brain development during prenatal exposure.   Axion's Maestro microelectrode array (MEA) system was one of the techniques investigating how methadone affects neuronal growth and neural network activity.  The authors were able to show a methadone dose-dependent suppression of firing of spontaneous action potentials and that this could be reversed with low-dosing.

Six week old cortical organoids were plated in Axion's 12-well plate and allowed to grow for 2 weeks before the onset of recording. Detection of spontaneous action potentials occurred from 8 weeks and the firing rate was calculated to quantify the neuronal network activity in the hCOs.  Methadone was added to the plate with different concentrations.  The recorded raster plots depicted the decrease in action potentials following treatments. Analysis of the firing rate showed a significant decrease after dosing with methadone. Higher doses resulted in an unrecoverable neurotoxicity and elimination of activity, while lower doses were able to recover after 7 days.