Induced neural progenitor cells and iPS-neurons from major depressive disorder patients show altered bioenergetics and electrophysiological properties

Julian Triebelhorn; Iseline Cardon; Kerstin Kuffner; Stefanie Bader; Tatjana Jahner; Katrin Meindl; Tanja Rothhammer-Hampl; Markus J. Riemenschneider; Konstantin Drexler; Mark Berneburg; Caroline Nothdurfter; André Manook; Christoph Brochhausen; Thomas C. Baghai; Sven Hilbert; Rainer Rupprecht; Vladimir M. Milenkovic; Christian H. Wetzel

doi:10.1038/s41380-022-01660-1

journal article Open Access Jun 22, 2022

Induced neural progenitor cells and iPS-neurons from major depressive disorder patients show altered bioenergetics and electrophysiological properties

Julian Triebelhorn

Iseline Cardon

Kerstin Kuffner Stefanie Bader Tatjana Jahner Katrin Meindl

Tanja Rothhammer-Hampl

Markus J. Riemenschneider Konstantin Drexler Mark Berneburg

Caroline Nothdurfter André Manook Christoph Brochhausen

Thomas C. Baghai Sven Hilbert

Rainer Rupprecht Vladimir M. Milenkovic Christian H. Wetzel

Molecular Psychiatry Vol. 29 No. 5 pp. 1217-1227 · Springer Science and Business Media LLC

View at Publisher Save 10.1038/s41380-022-01660-1

Abstract

Abstract

The molecular pathomechanisms of major depressive disorder (MDD) are still not completely understood. Here, we follow the hypothesis, that mitochondria dysfunction which is inevitably associated with bioenergetic disbalance is a risk factor that contributes to the susceptibility of an individual to develop MDD. Thus, we investigated molecular mechanisms related to mitochondrial function in induced neuronal progenitor cells (NPCs) which were reprogrammed from fibroblasts of eight MDD patients and eight non-depressed controls. We found significantly lower maximal respiration rates, altered cytosolic basal calcium levels, and smaller soma size in NPCs derived from MDD patients. These findings are partially consistent with our earlier observations in MDD patient-derived fibroblasts. Furthermore, we differentiated MDD and control NPCs into iPS-neurons and analyzed their passive biophysical and active electrophysiological properties to investigate whether neuronal function can be related to altered mitochondrial activity and bioenergetics. Interestingly, MDD patient-derived iPS-neurons showed significantly lower membrane capacitance, a less hyperpolarized membrane potential, increased Na
+
current density and increased spontaneous electrical activity. Our findings indicate that functional differences evident in fibroblasts derived from MDD patients are partially present after reprogramming to induced-NPCs, could relate to altered function of iPS-neurons and thus might be associated with the aetiology of major depressive disorder.

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Details

Published: Jun 22, 2022
Vol/Issue: 29(5)
Pages: 1217-1227
License: View

Authors

Tanja Rothhammer-Hampl

M

Markus J. Riemenschneider

Department of Neuropathology Regensburg University Hospital Regensburg Germany

Christoph Brochhausen

Institute of Pathology, University of Regensburg, Regensburg, Germany

Vladimir M. Milenkovic

C

Christian H. Wetzel

Funding

Deutsche Forschungsgemeinschaft Award: 422182557

Bundesministerium für Bildung und Forschung Award: 01EE1401B

Bayerische Forschungsstiftung Award: ForIPS

Else-Kröner-Fresenius-Stiftung

Cite This Article

Julian Triebelhorn, Iseline Cardon, Kerstin Kuffner, et al. (2022). Induced neural progenitor cells and iPS-neurons from major depressive disorder patients show altered bioenergetics and electrophysiological properties. Molecular Psychiatry, 29(5), 1217-1227. https://doi.org/10.1038/s41380-022-01660-1

Induced neural progenitor cells and iPS-neurons from major depressive disorder patients show altered bioenergetics and electrophysiological properties

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