Local calcium accumulations promote phagocyte-mediated synapse removal in cortical neuroinflammation

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https://rdp.sfb274.de/ (Research Data Platform) https://gepris.dfg.de/gepris/projekt/408885537 (DFG Gepris entry) The central nervous system (CNS) is a terminally differentiated tissue, where any insult carries a heightened risk - yet the tissue response to these insults is variable and can range from irreversible destruction to almost complete recovery. The rules that instruct these divergent outcomes are still unknown. The aim of this CRC is therefore to understand the biology of the multicellular ...

In multiple sclerosis, an “energy crisis”, which entails axonal ATP depletion, contributes to neuronal dysfunction and ensuing neurodegeneration. We have identified dysregulation of the TCA cycle and specifically depletion of its pacemaker enzyme, IDH3, as a critical checkpoint of neuronal energy homeostasis. Targeting IDH3, however, leads only to partial reversal of axonal ATP deficits, pointing to further neuroenergetic checkpoints. We now plan to identify these checkpoints and study their ...

Cortical pathology contributes to chronic cognitive impairment of patients suffering from the neuroinflammatory disease multiple sclerosis (MS). How such gray matter inflammation affects neuronal structure and function is not well understood. In the present study, we use functional and structural in vivo imaging in a mouse model of cortical MS to demonstrate that bouts of cortical inflammation disrupt cortical circuit activity coincident with a widespread, but transient, loss of dendritic spines. ...