Optimizing animal models of autoimmune encephalitis using active immunization.

Area of Science:

• Neuroscience
• Immunology
• Neurology

Background:

• Autoimmune encephalitis (AE) is a severe neurological disorder with significant morbidity and mortality.
• N-methyl-D-aspartic acid receptor (NMDAR) encephalitis (NMDARE) is the most common form of AE, characterized by NMDAR antibodies.
• Translational rodent models are crucial for studying AE pathophysiology and advancing diagnosis and treatment.

Purpose of the Study:

• To identify optimal active immunization conditions for creating a translational mouse model of NMDAR encephalitis.
• To compare different induction methods for developing NMDARE in mice.

Main Methods:

• Female C57BL/6J mice were immunized with a peptide targeting the NMDAR GluN1 subunit.
• Three induction methods were tested: ventral immunization, dorsal immunization, and boosted dorsal immunization.
• Measurements included NMDAR antibody titers, behavioral changes, hippocampal NMDAR density, and brain immune cell infiltration.

Main Results:

• All immunized mice developed NMDAR antibodies.
• Ventral immunization led to earlier onset of AE-like symptoms, including memory deficits and depressive behavior.
• Dorsal immunization with boosting resulted in higher antibody titers and was associated with memory dysfunction and anxiety in longer studies.

Conclusions:

• Induction method significantly impacts the development and characteristics of NMDARE mouse models.
• Ventral immunization provides an effective model for short-term NMDARE studies.
• Boosted dorsal immunization may be more suitable for long-term studies requiring a more durable immune response.