Brain, behavior, & immunity - health · 2026
NMDAR subunit GluN1 dynamics in urinary astrocyte-derived extracellular vesicles in anti-NMDAR encephalitis.
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Mei Junhua, Chen Mian-Mian, Yang Qing, Xu Shu-Xian, Wang Chao, Lyu Honggang, Gong Qian, Liu Zhongchun, Bullmore Edward, Lynall Mary-Ellen, Xie Xin-Hui
Аннотация
BACKGROUND AND OBJECTIVES: Longitudinal measurement in vivo of molecular changes in the central nervous system (CNS) is important to investigate and guide treatment of rapidly changing neurological diseases. Here, we show how a novel protocol for urinary astrocyte-derived extracellular vesicles (uADEVs) can be used non-invasively to track the dynamic trajectory of the N-methyl-D-aspartate receptor (NMDAR) subunit GluN1 in a patient with anti-NMDAR encephalitis.
METHODS: We collected 18 morning urine samples from the patient over 34 days of hospitalisation, as well as 15 samples from a healthy control. We isolated uADEVs, measured GluN1 concentrations, and used a wavelet transform to analyse the time-frequency dynamics of the GluN1 signal.
RESULTS: Compared with the control, GluN1 levels in the patient's uADEVs were higher on average and more variable over time. Wavelet analysis resolved (i) a low-frequency trend that decreased over time, matching the decrease of GluN1 in cerebrospinal fluid associated with clinical recovery; and (ii) a higher frequency oscillation, with GluN1 levels peaking about 48-72 hours after each of 4 cycles of methotrexate infusion.
CONCLUSION: This case study provides preliminary evidence that urinary ADEV sampling is feasible for measuring brain biomarker dynamics linked to the clinical course and treatment of auto-immune encephalitis.
METHODS: We collected 18 morning urine samples from the patient over 34 days of hospitalisation, as well as 15 samples from a healthy control. We isolated uADEVs, measured GluN1 concentrations, and used a wavelet transform to analyse the time-frequency dynamics of the GluN1 signal.
RESULTS: Compared with the control, GluN1 levels in the patient's uADEVs were higher on average and more variable over time. Wavelet analysis resolved (i) a low-frequency trend that decreased over time, matching the decrease of GluN1 in cerebrospinal fluid associated with clinical recovery; and (ii) a higher frequency oscillation, with GluN1 levels peaking about 48-72 hours after each of 4 cycles of methotrexate infusion.
CONCLUSION: This case study provides preliminary evidence that urinary ADEV sampling is feasible for measuring brain biomarker dynamics linked to the clinical course and treatment of auto-immune encephalitis.