INVESTIGATING THE ROLE OF THE GLUCOCORTICOID RECEPTOR IN OLIGODENDROCYTE PROGENITOR CELLS MICROGLIA INTERACTION

Chronic stress is known to impair nervous system function and memory and is associated with psychiatric disorders such as depression. These effects are largely mediated by glucocorticoids, including corticosterone. Although the neuropathological mechanisms underlying depression remain incompletely understood, altered neurotransmission and neuroinflammation are considered key contributing factors. Recent studies have demonstrated an important role of the signaling of the glucocorticoid receptor (GR), to which glucocorticoids bind, in oligodendrocyte progenitor cells (OPCs) for bidirectional communication with neurons and microglia. However, whether GR signaling in OPCs is required for regulating OPC–microglia interactions remains unclear. To address this question, we employ a conditional mouse model lacking the GR specifically in OPCs. Using multiplex immunofluorescence, we analyze OPC and microglia cell numbers as well as their spatial proximity to assess potential changes in cell–cell interactions. In parallel, behavioral assays are performed in the same animals. Ongoing experiments aim to characterize how OPC-specific GR deletion affects OPC and microglia proliferation and microglial activation states. We hypothesize that GR signaling in OPCs is not only essential for OPC–neuron communication but also plays a critical role in modulating OPC–microglia interactions, potentially promoting microglial reactivity and neuroinflammation under chronic stress conditions.