Role of cannabinoids in induced pluripotent stem cell-derived oligodendrocytes from schizophrenia patients

Abstract

The pathophysiology of schizophrenia (SCZ) is highly complex and involves several neurotransmission systems. Recently, the endocannabinoid system has been investigated in this field, and cannabinoids (endocannabinoids, phytocannabinoids and synthetic cannabinoids) seem to be a potential target to treat SCZ. Additionally, abnormalities in glia cells - especially oligodendrocytes (OLs) - play a key role in the disrupted brain communication observed in SCZ. Although endocannabinoid signaling and OL alterations are clearly involved in the pathophysiology of SCZ, no data have reported the interplay between these two components for SCZ. Following up on this knowledge gap, we have investigated this interaction in the OL cell line (MO3.13) with proteomic tools (Current PD project: FAPESP 2017/18242-1). We have found interesting results, but MO3.13 cells present some limitations such as the lack of a genotypic profile of schizophrenia. As such, studies on SCZ with induced pluripotent stem cells (iPSCs) have succeeded in the identification of alterations at molecular and cellular levels. To achieve this, the forced expression of specific transcriptions factors (SOX10, OLIG2, and NKX6.2) will be used to generate OLs. Thusly, the investigation of the role of cannabinoids on oligodendrocyte differentiation and other processes may elucidate aspects of the pathobiology of schizophrenia, and may substantiate these mechanisms as targets for future pharmacological approaches. Finally, studying the effects of cannabinoids on OL differentiation from human pluripotent stem cell-derived neural precursor cells will help to increase the knowledge about endocannabinoid signaling in this process, along with its implications in the white matter deficits observed in schizophrenia. (AU)