Valproate reverts zinc and potassium imbalance in schizophrenia-derived reprogrammed cells.

Schizophrenia has been considered a devastating clinical syndrome rather than a single disease. Nevertheless, the mechanisms behind the onset of schizophrenia have been only partially elucidated. Several studies propose that levels of trace elements are abnormal in schizophrenia; however, conflicting data generated from different biological sources prevent conclusions being drawn. In this work, we used synchrotron radiation X-ray microfluorescence spectroscopy to compare trace element levels in neural progenitor cells (NPCs) derived from two clones of induced pluripotent stem cell lines of a clozapine-resistant schizophrenic patient and two controls. Our data reveal the presence of elevated levels of potassium and zinc in schizophrenic NPCs. Neural cells treated with valproate, an adjunctive medication for schizophrenia, brought potassium and zinc content back to control levels. These results expand the understanding of atomic element imbalance related to schizophrenia and may provide novel insights for the screening of drugs to treat mental disorders.

Predifferentiated embryonic stem cells promote functional recovery after spinal cord compressive injury.

We tested the effects of mouse embryonic stem cells (mES) grafts in mice spinal cord injury (SCI). Young adult female C57/Bl6 mice were subjected to laminectomy at T9 and 1-minute compression of the spinal cord with a vascular clip. Four groups were analyzed: laminectomy (Sham), injured (SCI), vehicle (DMEM), and mES-treated (EST). mES pre-differentiated with retinoic acid were injected (8 x 10(5) cells/2 microl) into the lesion epicenter, 10 min after SCI. Basso mouse scale (BMS) and Global mobility test (GMT) were assessed weekly up to 8 weeks, when morphological analyses were performed. GMT analysis showed that EST animals moved faster (10.73+/-0.9076, +/-SEM) than SCI (5.581+/-0.2905) and DMEM (5.705+/-0.2848), but slower than Sham animals (15.80+/-0.3887, p<0.001). By BMS, EST animals reached the final phase of locomotor recovery (3.872+/-0.7112, p<0.01), while animals of the SCI and DMEM groups improved to an intermediate phase (2.037+/-0.3994 and 2.111+/-0.3889, respectively). White matter area and number of myelinated nerve fibers were greater in EST (46.80+/-1.24 and 279.4+/-16.33, respectively) than the SCI group (39.97+/-0.925 and 81.39+/-8.078, p<0.05, respectively). EST group also presented better G-ratio values when compared with SCI group (p<0.001). Immunohistochemical revealed the differentiation of transplanted cells into astrocytes, oligodendrocytes, and Schwann cells, indicating an integration of transplanted cells with host tissue. Ultrastructural analysis showed, in the EST group, better tissue preservation and more remyelination by oligodendrocytes and Schwann cells than the other groups. Our results indicate that acute transplantation of predifferentiated mES into the injured spinal cord increased the spared white matter and number of nerve fibers, improving locomotor function.