Immunoglobulins and Efgartigimod reduce neuronal activity in primary rat cortical neuron cultures

Immunoglobulin-based therapies are increasingly used to modulate neuroinflammatory diseases, yet it remains unclear whether they directly affect neuronal function. Here, we provide evidence that primary rat cortical neurons express both the inhibitory Fc gamma receptor IIb (FcγRIIb) and the neonatal Fc receptor (FcRn), as assessed by immunocytochemistry and mRNA analysis. FcγRIIb expression was upregulated under proinflammatory conditions, indicating inflammation-dependent regulation. Using microelectrode array recordings, we observed that immunoglobulin treatment reduced neuronal activity under both physiological and inflammatory conditions. Similarly, Efgartigimod, a high-affinity FcRn blocker, was associated with a sustained reduction in neuronal activity, with the observed effects suggesting a trend toward dose dependence under control conditions. Together, these findings provide proof-of-concept evidence that primary cortical neuronal cultures respond to immunoglobulins and Efgartigimod in vitro and highlight neuronal Fc receptor signaling as a promising avenue for future studies.