In vivo effects of GAD65-specific b78 antibody in the hippocampus

Anti-glutamate decarboxylase 65 (GAD65) antibodies bind the smaller isoform of GAD that converts the excitatory glutamate into inhibitory GABA at the level of GABAergic neurons. Their effects are epitope-specific. Indeed, it has been demonstrated that b78 recognizes an epitope located at the C-terminus (512-540) while the b96.11 target is located in the center of the protein (308-365). These two GAD65-specific human monoclonal antibodies derived from a patient with autoimmune polyendocrine syndrome type 1 have been isolated by the Laboratory of Christiane Hampe (University of Washington).

Anti-GAD65 antibodies have been detected in patients suffering from several diseases (stiff person syndrome, cerebellar ataxia, limbic encephalitis and type 1 diabetes) including some with cognitive deficits. Because the hippocampus is a brain structure essential in the storage process, evaluate the impact of these antibodies in the hippocampus could bring some new insights in the understanding of diseases.

Preliminary experiments carried out in the Laboratory of Neuroscience allowed to identify a defect in synaptic plasticity and a microglial proliferation in hippocampal organotypic cultures in the presence of b78 antibodies. So in this study we tend to verify these observations in vivo and to explore more deeply the specific effect of b78 and b96.11 GAD65-specific antibodies in the hippocampus.