Hyperdynamic microtubule-based structural changes in Monocyte-Derived-Neuronal-like cells from patients with schizophrenia

A consistent postmortem finding in schizophrenia (SCZ) is reduction in dendrites' size. However, neurons with larger dendritic trees have also been encountered. In vitro experiments with neurons and neuronal-like cells coming directly from patients with SCZ showed similar results, evidencing at times more extensions and at others less arborizations. The process of extending and retracting neuronal outgrowths depends on microtubules polymerization and depolymerization. The possibility that microtubule polymerization/depolymerization is related to defects in the neuronal structure comes from several microtubular anomalies reported in SCZ such as its abnormal distribution in the cytoplasm, irregular shape of microtubules and even absence of these cytoskeletal components in dendrites. Moreover, microtubules in olfactory neuroepithelial cells from patients with SCZ were resistant to depolymerization. But whether deficits in microtubules are associated with abnormalities in the neuronal structure has never been investigated in living cells coming directly from patients. Therefore, we studied dynamic neurostructural changes in Monocyte-Derived-Neuronal-like cells (MDNCs) from 12 controls and 13 patients with SCZ. First, we showed that human neuroprogenitor cells and MDNCs have comparable neurostructural plasticity. Then, we investigated whether colchicine, a microtubular stabilizing and depolymerizing agent, disrupts dynamic neurostructural changes. The lowest concentration of colchicine tested, stopped dynamic neurostructural changes in MDNCs from controls, while cells from patients with SCZ continued to extend and retract neuronal outgrowths. Following, we investigated if antipsychotics impact dynamic structural changes, but our results were inconclusive. Our data indicate that, under certain circumstances, neuronal-like cells from patients with SCZ evidenced hyperdynamic microtubule-based neurostructural changes and consequently, link deficits in microtubules with anomalies in the neuronal shape. While other potential confounders are unlikely to have influenced our results, the effects of medications cannot be excluded.