Aberrant neuronal connectivity and network activity of neurons derived from patients with idiopathic schizophrenia.

Autor: Heider J; NMI Natural and Medical Sciences Institute at the University of Tübingen, 72770 Reutlingen, Germany., González EP; NMI Natural and Medical Sciences Institute at the University of Tübingen, 72770 Reutlingen, Germany; International Max Planck Research School, Graduate Training Centre of Neuroscience, University of Tübingen, 72076 Tübingen, Germany., Hartmann SM; NMI Natural and Medical Sciences Institute at the University of Tübingen, 72770 Reutlingen, Germany; International Max Planck Research School, Graduate Training Centre of Neuroscience, University of Tübingen, 72076 Tübingen, Germany., Kannaiyan N; Department of Psychiatry and Psychotherapy, LMU University Hospital, LMU Munich, 80336 Munich, Germany., Vogel S; NMI Natural and Medical Sciences Institute at the University of Tübingen, 72770 Reutlingen, Germany., Wüst R; Department of Psychiatry, Tübingen Center for Mental Health (TüCMH), University of Tübingen, Tübingen, Germany; German Center for Mental Health (DZPG), Partner Site Tübingen, 72076 Tübingen, Germany., Fallgatter AJ; Department of Psychiatry, Tübingen Center for Mental Health (TüCMH), University of Tübingen, Tübingen, Germany; German Center for Mental Health (DZPG), Partner Site Tübingen, 72076 Tübingen, Germany., Rossner MJ; Department of Psychiatry and Psychotherapy, LMU University Hospital, LMU Munich, 80336 Munich, Germany., Kraushaar U; NMI Natural and Medical Sciences Institute at the University of Tübingen, 72770 Reutlingen, Germany., Volkmer H; NMI Natural and Medical Sciences Institute at the University of Tübingen, 72770 Reutlingen, Germany; International Max Planck Research School, Graduate Training Centre of Neuroscience, University of Tübingen, 72076 Tübingen, Germany; German Center for Mental Health (DZPG), Partner Site Tübingen, 72076 Tübingen, Germany. Electronic address: volkmer@nmi.de.
Jazyk: angličtina
Zdroj: Neurobiology of disease [Neurobiol Dis] 2024 Oct 15; Vol. 201, pp. 106678. Date of Electronic Publication: 2024 Sep 21.
DOI: 10.1016/j.nbd.2024.106678
Abstrakt: Schizophrenia (SCZ) is a psychiatric disorder with a strong genetic determinant. A major hypothesis to explain disease aetiology comprises synaptic dysfunction associated with excitatory-inhibitory imbalance of synaptic transmission, ultimately contributing to impaired network oscillation and cognitive deficits associated with the disease. Here, we studied the morphological and functional properties of a highly defined co-culture of GABAergic and glutamatergic neurons derived from induced pluripotent stem cells (iPSC) from patients with idiopathic SCZ. Our results indicate upregulation of synaptic genes and increased excitatory synapse formation on GABAergic neurons in co-cultures. In parallel, we observed decreased lengths of axon initial segments, concordant with data from postmortem brains from patients with SCZ. In line with increased synapse density, patch-clamp analyses revealed markedly increased spontaneous excitatory postsynaptic currents (EPSC) recorded from GABAergic SCZ neurons. Finally, MEA recordings from neuronal networks indicate increased strength of network activity, potentially in response to altered synaptic transmission and E-I balance in the co-cultures. In conclusion, our results suggest selective deregulation of neuronal activity in SCZ samples, providing evidence for altered synapse formation and synaptic transmission as a potential base for aberrant network synchronization.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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