MiR-132-3p promotes neuroinflammation and dopaminergic neurodegeneration by suppressing glutaredoxin expression.

This study aimed to investigate the effect of miR-132-3p/GLRX on neuroinflammation and dopaminergic neurodegeneration in Parkinson’s disease (PD). In clinical experiments, the levels of miR-132-3p and glutaredoxin (GLRX) in the midbrain tissuesfrom 5 patients with PD were analyzed by qRT-PCR and Western blotting. In cell experiments, inflammatory cell models were established by lipopolysaccharide (LPS) stimulation. miR-132-3p loss- and gain-of-function assays were carried out to investigate the function of miR-132-3p in the BV-2 cell inflammatory response and neuronal injury. RIP experiments and dual-luciferase reporter assays were used to verify the binding of miR-132-3p to GLRX. Gene cotransfection in rescue assays was used to confirm the role of miR-132-3p/GLRX in microglial cell activation and neuronal injury. In animal experiments, mouse models of PD were established by MPTP injection. The effect of miR-132-3p on neuroinflammation and dopaminergic neurodegeneration in mice with PD was explored with fluorescence in situ hybridization (FISH), immunofluorescence, and behavioral tests. The results showed increased miR-132-3p expression and decreased GLRX expression in the midbrain tissues of PD patients. Overexpression of miR-132-3p increased the expression of TNF-α, IL-1β and IL-6 in LPS-treated BV-2 cells, and after coculture with conditioned medium of BV-2 cells, SH-SY5Y cells exhibited increased apoptosis and decreased viability in response to miR-132-3p overexpression, while the opposite results were obtained in miR-132-3p-knockdown cells, indicating that miR-132-3p can promote microglial cell activation and enhance neuronal injury. GLRX was a target gene of miR-132-3p, and GLRX could abolish miR-132-3p-induced neuronal injury and microglial activation. Depletion of miR-132-3p ameliorated dopaminergic neuron degeneration and neuroinflammation in mice with PD. Conclusively, miR-132-3p promoted the activation of microglial cells and further facilitated the loss of dopaminergic neurons by negatively regulating GLRX expression.
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