PATHOLOGICAL IMPLICATIONS OF ANTI-GLUA3 ANTIBODIES IN FRONTOTEMPORAL DEMENTIA: FROM ANIMAL MODEL TO RESCUE STRATEGY
type: CreativeWork
description: Over the last two decades, growing attention has been paid to the role of autoantibodies that target brain antigens in disorders of the central nervous system. Within this field, several studies detected anti-GluA3 antibodies in the serum of patients with autoimmune encephalitis and epilepsy. More recently, our research group identified anti-GluA3 antibodies in 20%–25% of patients with frontotemporal dementia (FTD), introducing novel implications for a pathogenic role of glutamate receptor autoantibodies in neurodegenerative diseases. Although previous in vitro studies showed that anti-GluA3 autoantibodies affect glutamatergic neurotransmission through different mechanisms, the impact of these autoantibodies on cognitive and social functions in vivo is still unknown, as well as the biological substrates of these putative modifications. To address this gap of knowledge and better dissect the contribution of anti-GluA3 autoantibodies to the above-mentioned neurological conditions, in the present study, we employed two models of in vivo administration of anti-GluA3 antibodies isolated from patients (anti-GluA3 hIgGs) to mice. First, we demonstrated that a single injection of anti-GluA3 hIgGs into the lateral ventricles induced profound molecular and morphological alterations into the prefrontal cortex of mice. Accordingly, mice presented significant changes in recognition memory and impairments in social behavior and in social cognitive functions. Given the negative effects of acute GluA3 hIgGs administration on synapses, behavior, and cognition, whether and how the chronic presence of autoantibodies triggers a neurodegenerative process and the association between this process and the appearance of FTD-related neuropathological and behavioral signature should be further investigated. Thus, we developed a chronic model by infusing mice with anti-GluA3 hIgGs for one month through an intracerebroventricular cannula. Data showed that chronic anti-GluA3 hIgGs administration…
abstract: Over the last two decades, growing attention has been paid to the role of autoantibodies that target brain antigens in disorders of the central nervous system. Within this field, several studies detected anti-GluA3 antibodies in the serum of patients with autoimmune encephalitis and epilepsy. More recently, our research group identified anti-GluA3 antibodies in 20%–25% of patients with frontotemporal dementia (FTD), introducing novel implications for a pathogenic role of glutamate receptor autoantibodies in neurodegenerative diseases. Although previous in vitro studies showed that anti-GluA3 autoantibodies affect glutamatergic neurotransmission through different mechanisms, the impact of these autoantibodies on cognitive and social functions in vivo is still unknown, as well as the biological substrates of these putative modifications. To address this gap of knowledge and better dissect the contribution of anti-GluA3 autoantibodies to the above-mentioned neurological conditions, in the present study, we employed two models of in vivo administration of anti-GluA3 antibodies isolated from patients (anti-GluA3 hIgGs) to mice. First, we demonstrated that a single injection of anti-GluA3 hIgGs into the lateral ventricles induced profound molecular and morphological alterations into the prefrontal cortex of mice. Accordingly, mice presented significant changes in recognition memory and impairments in social behavior and in social cognitive functions. Given the negative effects of acute GluA3 hIgGs administration on synapses, behavior, and cognition, whether and how the chronic presence of autoantibodies triggers a neurodegenerative process and the association between this process and the appearance of FTD-related neuropathological and behavioral signature should be further investigated. Thus, we developed a chronic model by infusing mice with anti-GluA3 hIgGs for one month through an intracerebroventricular cannula. Data showed that chronic anti-GluA3 hIgGs administration…
author: ITALIA, MARIA
language: eng
date published: 2024-01-19
date modified: 2026-07-27T20:19:03Z
provider: Università degli Studi di Milano
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Università degli Studi di Milano

PropertyValue
property ID: Handle
value: https://hdl.handle.net/2434/1022510

PropertyValue
property ID: DOI
value: 10.13130/italia-maria_phd2024-01-19