Diminished motor neuron activity driven by abnormal astrocytic GLAST glutamate transporter activity in spinal muscular atrophy is not fully restored after lentiviral SMN delivery

Authors: Welby E, Ebert AD.

Glia, 2022

Scientists use Axion’s Maestro MEA system to explore the impact of astrocyte-mediated disease mechanisms on motor neuron function in spinal muscular atrophy in vitro. 

Some evidence suggests that astrocytes play an important role in the genetic motor neuron disease spinal muscular atrophy (SMA), but this relationship is not fully understood. In this study, scientists use a human induced pluripotent stem cell (hiPSC)-derived model on Axion’s noninvasive, label-free Maestro microelectrode array system to investigate how glutamate transporter (GLAST) problems in astrocytes may contribute to survival motor neuron (SMN) deficiency and SMA. Overall, the findings demonstrate    that astrocytes poorly regulate glutamatergic synapses and that SMA motor neurons show control-levels of activity when cultured with healthy astrocytes but have poor activity when cultured with hiPSC SMA patient-derived astrocytes. According to the authors, the results may have important implications for SMA therapeutics, writing “As novel therapies for SMA progress and long-term effects of FDA-approved treatments are assessed in patients, our work highlights the importance of early therapeutic intervention to promote glial cell health and tracking improvements in glial-mediated neuromodulation, which may be critical to fully restore sensory-motor circuit functionality.”