Induced neural progenitor cells and iPS-neurons from major depressive disorder patients show altered bioenergetics and electrophysiological properties.
Journal
Molecular psychiatry
ISSN: 1476-5578
Titre abrégé: Mol Psychiatry
Pays: England
ID NLM: 9607835
Informations de publication
Date de publication:
22 Jun 2022
22 Jun 2022
Historique:
received:
20
05
2021
accepted:
07
06
2022
revised:
30
05
2022
entrez:
22
6
2022
pubmed:
23
6
2022
medline:
23
6
2022
Statut:
aheadofprint
Résumé
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
Identifiants
pubmed: 35732695
doi: 10.1038/s41380-022-01660-1
pii: 10.1038/s41380-022-01660-1
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : 422182557
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : GRK2174
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : GRK2174
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : GRK2174
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : GRK2174
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : GRK2174
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : 422182557
Organisme : Bayerische Forschungsstiftung (Bavarian Research Foundation)
ID : ForIPS
Organisme : Bayerische Forschungsstiftung (Bavarian Research Foundation)
ID : ForInter
Organisme : Bayerische Forschungsstiftung (Bavarian Research Foundation)
ID : ForIPS
Organisme : Bayerische Forschungsstiftung (Bavarian Research Foundation)
ID : ForInter
Organisme : Bundesministerium für Bildung und Forschung (Federal Ministry of Education and Research)
ID : 01EE1401B
Organisme : Bundesministerium für Bildung und Forschung (Federal Ministry of Education and Research)
ID : 01EE1401B
Informations de copyright
© 2022. The Author(s).
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