Upregulation of brain-enriched miR-107 promotes excitatory neurotoxicity through downregulation of glutamate transporter 1 expression following ischemic stroke

In this study, we screened the expressions of 9 brain-specific or brain-enriched miRNAs in a focal cerebral ischemia/reperfusion (I/R) injury rat model, which showed glutamate accumulation and down-regulated GLT-1 expression as expected, and uncovered miR-107 level was elevated in both brain tissue and plasma in the model. Next, we examined the functional relationship of miR-107 with GLT-1 expression in a nerve cell hypoxia/reoxygenation (H/R) injury model. H/R treatment increased apoptosis of the nerve cells concomitant with glutamate accumulation, miR-107 elevation and suppressed GLT-1 expression, mimicking our in vivo findings in the cerebral I/R injury rat model in vitro. Co-treating the cells with a miR-107 inhibitor blocked all the effects, demonstrating that miR-107 functions to inhibit GLT-1 expression and elevate glutamate accumulation. To extend these animal and cell-based studies to clinical patients, we measured the plasma levels of miR-107 and glutamate, and observed that both miR-107 and glutamate were elevated in ischemic stroke patients. Based on these observations, we conclude that elevated miR-107 expression after ischemic stroke accounts, at least partially, for the glutamate accumulation through suppression of GLT-1 expression. Our findings also highlight that the plasma level of miR-107 may serve as a novel biomarker for monitoring excitotoxicity in the ischemic stroke patients.
Source: Clinical Science - Category: Biomedical Science Authors: Source Type: research