Abstract:
The GluN1 subunit of the N-methyl-D-aspartate receptor (NMDAR) has been found to dissociate during stroke and enter normal circulation. Here it is identified as foreign by the immune system and has antibodies raised against it. Recent literature has identified the presence of antibodies raised against different sections of the, as well as the whole, GluN1 subunit in humans post stroke. Rats vaccinated against regions of and whole GluN1 proteins develop antibodies against each region. These antibodies have been shown in previous studies to affect cell counts in vitro. Using both rat raised antibodies and human serum samples post stroke, the effect of these antibodies were tested on rat hippocampal cells. The aim of this study was to address whether targeting of different epitopes by NR1 antibodies alters NMDA receptor function that might lead to effects on cell viability and plasticity. RecNR1 treated cells as well as human samples with high anti-GluN1 content showed conservation of neuron counts and dendritic processes compared to naïve treated cells. NR1NTD and human samples with high anti-NTD GluN1 content showed statistically significant toxicity in the form of neuron count loss and reduced dendritic area compared to naïve as well as high RecNR1/GluN1 samples. We have therefore identified the presence of two functional sections of the GluN1 subunit in stroke patients and identified specific roles for each in neuronal viability. It was concluded that high quantities of anti-GluN1 antibodies in the absence of antibodies raised against the N-terminus section provide a degree of protection of neurons that we would hypothesize to assist in the post-stroke recovery process. Future investigations into enhancing production of GluN1 antibodies or the inhibition of anti-NTD GluN1 antibodies may provide a future therapeutic option in stroke recovery.
