好色先生

好色先生

Explore the latest content from across our publications
Join The AAN

Log In

Forgot Password?
Create New Account

Loading... please wait

Abstract Details

Cerebroventricular infusion of patients’ antibodies cause memory loss and anxiety in a mice model of anti-metabotropic glutamate receptor 5 (mGluR5) encephalitis
Autoimmune Neurology
S21 - Autoimmune Neurology: Novel Diagnostic and Predictive Biomarkers and Immunopathologic Mechanisms of Disease (3:30 PM-3:41 PM)
001
To study the effects of patients’ antibodies targeting the metabotropic glutamate receptor 5 (mGluR5) on memory and behavior in mice.

Antibodies to mGluR5 have been reported in patients with autoimmune encephalitis manifesting with behavioral changes, memory deficits and anxiety. A direct pathogenic role of these antibodies has been suggested by the observation that they bind to the surface of cultured live neurons and cause a decrease of mGluR5. However, whether these antibodies can affect behavior and memory in animals is unknown. 
C57BL/6J mice received a 14-day continuous cerebroventricular infusion of IgG purified from serum of patients or healthy controls. During and after the infusion period, mice underwent standardized tests to assess memory (novel object location, at days 3, 10, 18, 25 from start of IgG infusion), anxiety (black and white, open field, at days 12 and 25, respectively) and locomotor activity (at days 3, 10, 18, 25). Animals were sacrificed at days 12 and 28 and their hippocampi were examined for antibodies effects on mGluR5 cluster density quantified by confocal imaging. 
Animals infused with patients’ IgG, but not with control IgG, showed progressive memory loss and increased anxiety, with preserved locomotor activity. These alterations started at day 3, worsened at day 12 and progressively recovered by day 25. Preliminary data from hippocampi of mice infused with patient’s antibodies, but not with control IgG, showed a decrease of mGluR5 cluster density at day 12, which was substantially recovered (although not to baseline levels) at day 28.
Patients’ IgG cause significant and reversible alterations of memory and anxiety in mice, correlating with changes in hippocampal mGluR5 cluster density. These findings suggest a link between behavioral/molecular alterations and mGluR5 antibodies, and support a pathogenic role for these antibodies in anti-mGluR5 encephalitis
Authors/Disclosures
Marianna Spatola, MD, PhD (FUNDACIÓ DE RECERCA BIOMEDICA CLÍNIC IDIBAPS)
PRESENTER 		The institution of Dr. Spatola has received research support from Spanish National Health Institute (Carlos III), FIS grant. The institution of Dr. Spatola has received research support from Spanish National Institute of Health - Miguel Servet Grant. The institution of Dr. Spatola has received research support from La Caixa Foundation.
No disclosure on file
No disclosure on file
No disclosure on file
No disclosure on file
Sonali Singh No disclosure on file
Myrna R. Rosenfeld, MD, PhD, FAAN (University of Barcelona) Dr. Rosenfeld has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Springer Nature. An immediate family member of Dr. Rosenfeld has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for 好色先生. Dr. Rosenfeld has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for Lamson Dugan & Murray LLP. The institution of an immediate family member of Dr. Rosenfeld has received research support from Sage Therapeutics. The institution of an immediate family member of Dr. Rosenfeld has received research support from Edmond J. Safra Foundation. The institution of an immediate family member of Dr. Rosenfeld has received research support from La Caixa Foundation. The institution of an immediate family member of Dr. Rosenfeld has received research support from Spanish Ministry of Health. The institution of an immediate family member of Dr. Rosenfeld has received research support from Department of Health, Government of Catalunya. Dr. Rosenfeld has received intellectual property interests from a discovery or technology relating to health care. An immediate family member of Dr. Rosenfeld has received intellectual property interests from a discovery or technology relating to health care. Dr. Rosenfeld has received intellectual property interests from a discovery or technology relating to health care. An immediate family member of Dr. Rosenfeld has received intellectual property interests from a discovery or technology relating to health care. Dr. Rosenfeld has received publishing royalties from a publication relating to health care. An immediate family member of Dr. Rosenfeld has received publishing royalties from a publication relating to health care. Dr. Rosenfeld has received publishing royalties from a publication relating to health care. An immediate family member of Dr. Rosenfeld has received publishing royalties from a publication relating to health care.
Josep O. Dalmau, MD, PhD, FAAN Dr. Dalmau has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Astellas Research Institute of America. Dr. Dalmau has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Janssen Research & Development . Dr. Dalmau has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for 好色先生. An immediate family member of Dr. Dalmau has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Springer Nature. The institution of Dr. Dalmau has received research support from Sage Therapeutics. The institution of Dr. Dalmau has received research support from Edmond J.Safra Foundation . The institution of Dr. Dalmau has received research support from La Caixa Foundation. The institution of Dr. Dalmau has received research support from Spanish Ministry of Health (ISCIII). The institution of Dr. Dalmau has received research support from Euroimmun, Inc. Dr. Dalmau has received intellectual property interests from a discovery or technology relating to health care. An immediate family member of Dr. Dalmau has received intellectual property interests from a discovery or technology relating to health care. Dr. Dalmau has received intellectual property interests from a discovery or technology relating to health care. An immediate family member of Dr. Dalmau has received intellectual property interests from a discovery or technology relating to health care. Dr. Dalmau has received publishing royalties from a publication relating to health care. Dr. Dalmau has received publishing royalties from a publication relating to health care. Dr. Dalmau has received publishing royalties from a publication relating to health care.