Induced neural progenitor cells and iPS-neurons from major depressive disorder patients show altered bioenergetics and electrophysiological properties
Induced neural progenitor cells and iPS-neurons from major depressive disorder patients show altered bioenergetics and electrophysiological properties
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 analysed 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, might relate to altered function of iPS-neurons and thus might be associated with the aetiology of major depressive disorder.
Triebelhorn Julian、Baghai Thomas C.、Hilbert Sven、Wetzel Christian H.、Cardon Iseline、Meindl Katrin、Rothhammer-Hampl Tanja、Rupprecht Rainer、Riemenschneider Markus J.、Kuffner Kerstin、Manook Andr¨|、Jahner Tatjana、Berneburg Mark、Drexler Konstantin、Milenkovic Vladimir M.、Nothdurfter Caroline、Bader Stefanie、Brochhausen Christoph
Department of Psychiatry and Psychotherapy, University of RegensburgDepartment of Psychiatry and Psychotherapy, University of RegensburgInstitute of Educational Research, Faculty of Human Sciences, University of RegensburgDepartment of Psychiatry and Psychotherapy, University of RegensburgDepartment of Psychiatry and Psychotherapy, University of RegensburgDepartment of Psychiatry and Psychotherapy, University of RegensburgDepartment of Neuropathology, Regensburg University HospitalDepartment of Psychiatry and Psychotherapy, University of RegensburgDepartment of Neuropathology, Regensburg University HospitalDepartment of Psychiatry and Psychotherapy, University of RegensburgDepartment of Psychiatry and Psychotherapy, University of RegensburgDepartment of Psychiatry and Psychotherapy, University of RegensburgDepartment of Dermatology, Regensburg University HospitalDepartment of Dermatology, Regensburg University HospitalDepartment of Psychiatry and Psychotherapy, University of RegensburgDepartment of Psychiatry and Psychotherapy, University of RegensburgDepartment of Psychiatry and Psychotherapy, University of RegensburgInstitute of Pathology, University of Regensburg||Central Biobank of the University of Regensburg and the Regensburg University Hospital
神经病学、精神病学基础医学分子生物学
Triebelhorn Julian,Baghai Thomas C.,Hilbert Sven,Wetzel Christian H.,Cardon Iseline,Meindl Katrin,Rothhammer-Hampl Tanja,Rupprecht Rainer,Riemenschneider Markus J.,Kuffner Kerstin,Manook Andr¨|,Jahner Tatjana,Berneburg Mark,Drexler Konstantin,Milenkovic Vladimir M.,Nothdurfter Caroline,Bader Stefanie,Brochhausen Christoph.Induced neural progenitor cells and iPS-neurons from major depressive disorder patients show altered bioenergetics and electrophysiological properties[EB/OL].(2025-03-28)[2025-05-19].https://www.biorxiv.org/content/10.1101/2021.04.30.441774.点此复制
评论