Astroglioma conditioned medium increases synaptic elimination and correlates with major histocompatibility complex of class I (MHC I) upregulation in PC12Cells

Astrocytes are multifunctional glial cells that actively participate in synaptic plasticity in health and disease. Little is known about molecular interactions between neurons and glial cells that result in synaptic stability or elimination. In this sense, the main histocompatibility complex of class I (MHC I) has been shown to play a role in the synaptic plasticity process during development and after lesion of the CNS. MHC I levels in neurons appear to be influenced by astrocyte secreted molecules, which may generate endoplasmic reticulum stress. In vitro studies are of relevance since cell contact can be avoided by the use of astrocyte conditioned medium, allowing investigation of soluble factors isolated from cell direct interaction. Thus, we investigated synaptic preservation by synaptophysin and MHC I immunolabeling in PC12 neuron-like cells exposed to NG97 astroglioma conditioned medium (CM). For that, PC12 cells were cultured and differentiated into neuron-like profile with nerve growth factor. MHC I was induced with interferon beta treatment (IFN), and the effects were compared to PC12 exposure to NG97 CM. Overall, the results show that NG97 CM increases, more than IFN alone, the expression of MHC I, negatively influencing synaptic stability. This indicates that glial soluble factors influence synapse elimination, compatible to in vivo synaptic stripping process, in a cell contact independent fashion. In turn, our results indicate that deleterious effects of astroglioma are not only restricted to rapid growth ratio of the tumor, but also correlated with secretion of stress-related molecules that directly affect neuronal networks. (C) 2016 Elsevier Ireland Ltd. All rights reserved.