GluA3 autoantibodies induce alterations in dendritic spine and behavior in mice

Brain Behav Immun. 2021 Jul 8:S0889-1591(21)00265-8. doi: 10.1016/j.bbi.2021.07.001. Online ahead of print.ABSTRACTAutoantibodies targeting the GluA3 subunit of AMPA receptors (AMPARs) have been found in patients with Rasmussen's encephalitis and different types of epilepsy and were associated with the presence of learning and attention deficits. Our group recently identified the presence of anti-GluA3 immunoglobulin G (IgG) in about 25% of patients with frontotemporal dementia (FTD), thus suggesting a novel pathogenetic role also in chronic neurodegenerative diseases. However, the in vivo behavioral, molecular and morphological effects induced these antibodies are still unexplored. We injected anti-GluA3 IgG purified from the serum of FTD patients, or control IgG, in mice by intracerebroventricular infusion. Biochemical analyses showed a reduction of synaptic levels of GluA3-containing AMPARs in the prefrontal cortex (PFC), and not in the hippocampus. Accordingly, animals injected with anti-GluA3 IgG showed significant changes in recognition memory and impairments in social behavior and in social cognitive functions in mice. As visualized by confocal imaging, functional outcomes were paralleled by profound alterations of dendritic spine morphology in the prefrontal cortex. All observed behavioral, molecular and morphological alterations were transient and not detected 10-14 days from anti-GluA3 IgG injection. Overall, our in vivo preclinical data provide novel insights into ...
Source: Brain, Behavior, and Immunity - Category: Neurology Authors: Source Type: research