Triebelhorn, Julian and Cardon, Iseline and Kuffner, Kerstin and Bader, Stefanie and Jahner, Tatjana and Meindl, Katrin and Rothhammer-Hampl, Tanja and Riemenschneider, Markus J. and Drexler, Konstantin and Berneburg, Mark and Nothdurfter, Caroline and Manook, Andre and Brochhausen, Christoph and Baghai, Thomas C. and Hilbert, Sven and Rupprecht, Rainer and Milenkovic, Vladimir M. and Wetzel, Christian H. (2022) Induced neural progenitor cells and iPS-neurons from major depressive disorder patients show altered bioenergetics and electrophysiological properties. MOLECULAR PSYCHIATRY. ISSN 1359-4184, 1476-5578
Full text not available from this repository. (Request a copy)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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | PLURIPOTENT STEM-CELLS; MITOCHONDRIAL RESPIRATION; CAPACITANCE MEASUREMENTS; GENERATION; CONNECTIVITY; METHYLATION; PLATELETS; NETWORK; MODEL |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Dermatologie und Venerologie Medicine > Abteilung für Neuropathologie Medicine > Lehrstuhl für Pathologie Medicine > Lehrstuhl für Psychiatrie und Psychotherapie Human Sciences > Institut für Bildungswissenschaft > Professur für Methoden der empirischen Bildungsforschung - Prof. Dr. Sven Hilbert |
| Depositing User: | Petra Gürster |
| Date Deposited: | 01 Sep 2023 06:59 |
| Last Modified: | 01 Sep 2023 06:59 |
| URI: | https://pred.uni-regensburg.de/id/eprint/56453 |
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