GluA3 autoantibodies induce alterations in dendritic spine and behavior in mice

Autoantibodies targeting the GluA3 subunit of AMPA receptors (AMPARs) have been found in patients with Rasmussen’s encephalitis and different types epilepsy were associated presence learning attention deficits. Our group recently identified anti-GluA3 immunoglobulin G (IgG) about 25% frontotemporal dementia (FTD), thus suggesting a novel pathogenetic role also chronic neurodegenerative diseases. However, vivo behavioral, molecular morphological effects induced these antibodies are still unexplored. We injected IgG purified from serum FTD patients, or control IgG, mice by intracerebroventricular infusion. Biochemical analyses showed reduction synaptic levels GluA3-containing AMPARs prefrontal cortex (PFC), not hippocampus. Accordingly, animals significant changes recognition memory impairments social behavior cognitive functions. As visualized confocal imaging, functional outcomes paralleled profound alterations dendritic spine morphology PFC. All observed transient detected 10–14 days injection. Overall, our preclinical data provide insights into autoimmune indicate an additional pathological mechanism affecting excitatory synapses carrying that could contribute to clinical symptoms.