Authors: Shani Stern, Lei Zhang, Meiyan Wang, Rebecca Wright, Idan Rosh, Yara Hussein, Tchelet Stern, Ashwani Choudhary, Utkarsh Tripathi, Patrick Reed, Hagit Sadis, Ritu Nayak, Aviram Shemen, Karishma Agarwal, Diogo Cordeiro, David Peles, Yuqing Hang, Ana P. D. Mendes, Tithi D. Baul, Julien G. Roth, Shashank Coorapati, Marco P. Boks, W. Richard McCombie, Hilleke Hulshoff Pol, Kristen J. Brennand, János M. Réthelyi, René S. Kahn, Maria C. Marchetto and Fred H. Gage
Molecular Psychiatry, 04 May 2024
Researchers use Maestro MEA to investigate hippocampal synaptic deficits in schizophrenia.
Human stem cell research is advancing the understanding of schizophrenia, but due to genetic heterogeneity, the underlying mechanisms of the disease remain unclear. In this study, scientists used Axion Biosystems’ hands-free Maestro MEA and other methods to compare induced pluripotent stem cell (iPSC)-derived neurons from monozygotic twins discordant for schizophrenia and controls to investigate schizophrenia phenotypes with minimal genetic diversity. Maestro MEA results demonstrated that neurons derived from affected twins exhibited decreased numbers of spikes, bursts, and network bursts. Interestingly, neurons from unaffected twins also exhibited increased numbers of spikes and bursts, possibly representing a protective compensatory mechanism. Overall, the authors report that their findings ”point to hippocampal synaptic deficits as a central mechanism in schizophrenia,” and note that the deficits “appear when the cells are approximately 8 weeks after the start of the differentiation which means that these are still pre-natal neurons and this means that the patients are biologically predisposed [sic] to the disease.”
