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Mitochondrial ATP production is impaired in neural stem/progenitor cells derived from olfactory neuroepithelium of patients with schizophrenia

Published online by Cambridge University Press:  13 August 2021

C. Idotta ,
E. Tibaldi ,
N. Favaretto ,
M. Pagano ,
R. Peruzzo ,
G. Pigato ,
D. Cazzador ,
P. Meneguzzo ,
M. Solmi  and
L. Leanza
...Show all authors
C. Idotta*
Affiliation:
Molecular Medicine, University of Padua, Padua, Italy
E. Tibaldi
Affiliation:
Molecular Medicine, University of Padua, Padua, Italy
N. Favaretto
Affiliation:
Department Of Neuroscience, University of Padova, padova, Italy
M. Pagano
Affiliation:
Molecular Medicine, University of Padua, Padua, Italy
R. Peruzzo
Affiliation:
Biology, University of Padua, Padua, Italy
G. Pigato
Affiliation:
Psychiatry Clinic, Azienda Ospedaliera di Padova, Padua, Italy
D. Cazzador
Affiliation:
Department Of Neuroscience, University of Padova, padova, Italy
P. Meneguzzo
Affiliation:
Molecular Medicine, University of Padua, Padua, Italy
M. Solmi
Affiliation:
Padua Neuroscience Center, University of Padua, Padua, Italy
L. Leanza
Affiliation:
Biology, University of Padua, Padua, Italy
A. Favaro
Affiliation:
Department Of Neuroscience, University of Padova, padova, Italy
A.M. Brunati
Affiliation:
Molecular Medicine, University of Padua, Padua, Italy
T. Toffanin
Affiliation:
Psychiatry Clinic, Azienda Ospedaliera di Padova, Padua, Italy
*
*Corresponding author.

Abstract

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Introduction

Neural stem/progenitor cells derived from olfactory neuroepithelium (hereafter OE-NS/PCs) are emerging as a viable proxy and a valuable tool for translational studies on severe mental illnesses (SMI). In this respect, the use of OE-NS/PCs as a surrogate cellular model of schizophrenia (SZ) has enabled insights into cell signaling and cell cycle dynamics in this disease.

Objectives

We explored whether mitochondrial dysfunction, which has been already associated with SZ, may have a role in the altered proliferation pattern previously observed in OE-NS/PCs of SZ patients.

Methods

OE-NS/PCs were collected from 20 patients and 20 healthy controls (Hcs) by nasal brushing, cultured in proper medium and expanded. Fresh OE-NS/PCs at passage 3 of both groups underwent BrdU proliferation assays or were frozen for later use. Mitochondrial ATP production was measured in both fresh and thawed OE-NS/PCs by using the ATPlite Luminescence Assay kit.

Results

Fresh OE-NS/PCs of patients grew at a higher rate than those of HCs (M-W U=0; p<0.001), whereas the proliferation of thawed OE-NS/PCs of both groups exhibited an opposed pattern (at passage 6, p=0.002). Mitochondrial ATP production was significantly lower in OE-NS/PCs of patients than in those of HCs (M-W U=0; p=0.02), regardless of freeze-thaw conditions (M-W U=6; p=0.77).

Conclusions

Mitochondrial ATP production is negatively affected in OE-NS/PCs of SZ patients as compared to those of HCs. This evidence does not differ in fresh OE-NS/PCs and OE-NS/PCs undergoing freeze-thaw cycles, which instead perturb the proliferation pattern of SZ OE-NS/PCs.

Keywords

cellular modelsmitochondriaschizophréniatranslational psychiatry
Type
Abstract
Information
European Psychiatry , Volume 64 , Special Issue S1: Abstracts of the 29th European Congress of Psychiatry , April 2021 , pp. S383
Creative Commons
Creative Common License - CCCreative Common License - BY
This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited.
Copyright
© The Author(s), 2021. Published by Cambridge University Press on behalf of the European Psychiatric Association
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