The dynamics of glutamate receptor subunit GluN1 concentration in urinary astrocyte-derived extracellular vesicles from a patient with anti-NMDAR encephalitis
Mei, J.; Chen, M.-m.; Yang, Q.; Xu, S.-x.; Wang, C.; Lyu, H.; Gong, Q.; Liu, Z.; Bullmore, E.; Lynall, M.-E.; Xie, X.
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Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis involves dynamic changes in glutamatergic signalling. Magnetic resonance spectroscopy can monitor these changes but lacks temporal resolution and cell-type specificity. We investigated whether urinary astrocyte-derived extracellular vesicles (ADEVs) could serve as a non-invasive proxy for brain receptor dynamics. We prospectively collected longitudinal urine and cerebrospinal fluid (CSF) samples from a 30- 35-year-old female patient during 34 days of treatment. We isolated ADEVs using a specific protocol and measured GluN1 protein levels. A 30-35-year-old healthy female provided control samples. Wavelet transform analysis of the patient's GluN1 time series revealed two distinct patterns. First, a low-frequency trend showed declining GluN1 levels over the treatment period, which mirrored the reduction in CSF GluN1 concentrations. Second, a high-frequency oscillation appeared to be coupled with methotrexate infusions, with GluN1 peaks occurring approximately 48 hours after each dose. This secondary increase may reflect drug-induced p53 activation, which promotes the exosomal release of internalised receptors. These findings suggest that urinary ADEVs provide a feasible and informative method to monitor real-time molecular fluxes in the brain.
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