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

Abstract

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 models
• mitochondria
• schizophrénia
• translational psychiatry