Authors: Wu HF, Yu W, Saito-Diaz K, Huang CW, Carey J, Lefcort F, Hart GW, Liu HX, Zeltner N
Nature Communications, 13, 7032, 2022
Scientists use Axion’s Maestro Pro multielectrode array platform to investigate the function of sympathetic neurons in vitro in real time.
The use of human induced pluripotent stem cells (hiPSCs) is facilitating the study of familial dysautonomia (FD)—a rare neurodevelopmental and neurodegenerative genetic disorder that affects the sympathetic and peripheral nervous systems and can lead to life-threatening dysautonomic crises and cardiac instability—but scientists do not fully understand how FD impacts neural function. In this study, researchers model FD with patient-derived hPSC sympathetic neurons and use Axion’s Maestro Pro multielectrode array (MEA) platform to demonstrate that FD neurons are spontaneously hyperactive in vitro; primary neurons from FD mice were also found to be hyperactive via MEA. The team also used a neuron-cardiomyocyte co-culture to demonstrate neuromuscular innervation and increased beat rate in FD co-cultures, suggesting these neurons have the capacity to innervate and regulate cardiac activity.
Finally, the scientists identified norepinephrine transporter deficiency as a potential mechanism and used the FD model for drug screening and drug testing, finding that some compounds were able to reduce neural hyperactivity. The authors conclude that these findings may hold promise for the development of novel therapeutics in the future for FD and other disorders associated with the sympathetic nervous system.