Inflammatory intracellular signaling in neurons is influenced by glial soluble factors in iPSC-based cell model of PARK2-associated Parkinson's disease

Neuroinflammation is considered one of the driving factors in Parkinson's disease (PD). Astrocytes affect the function of neurons in different ways, of which humoral interactions are very important. Here, we used neuronal and glial cell cultures differentiated from iPSC of healthy donors (HD) and PD patients with different PARK2 mutations (PD) in order to evaluate the influence of glial secretome on inflammatory gene network in neurons and to estimate the impact of the lack of Parkin to this interaction. Overall design: iPSCs obtained from HD and from PD patient with PARK2-mutation (hom EX8 del PARK2) underwent the full course of differentiation into mature neurons. iPSCs obtained from 2 healthy donors and 2 patients with PARK2-associated PD underwent the full course of differentiation in glial direction. Further, neurons were cultivated in conditioned media obtained from glial cultures in four possible combinations: HD neurons in the conditioned medium from HD astrocytes (HD2), PD neurons in the conditioned medium from HD astrocytes (PD2), HD neurons in the conditioned medium from PD astrocytes (HD3), and PD neurons in the conditioned medium from PD astrocytes (PD3). The HD and PD neurons in the base neuronal culture medium (HD0, PD0), and HD and PD neurons in the base glial culture medium (HD1, PD1) were used as a control.