Inhibition of BDNF production by MPP+ through up-regulation of miR-210-3p contributes to dopaminergic neuron damage in MPTP model

The neurotrophin brain-derived neurotrophic factor (BDNF) has been involved in supporting of neuron survival. The observation of reduced level of BDNF in the substantia nigra (SN) of Parkinson's disease (PD) patients suggests its important role in neuron protection in PD pathogenesis. However, the mechanism underlying the down-regulation of BDNF in PD was largely unknown. In this study, we found that miR-210-3p is involved in the regulation of BDNF production by 1-methyl-4-phenylpyridinium (MPP+). MPP+ inhibits the BDNF production in SH-SY5Y cells through a transcription independent manner. Moreover, miR-210-3p, which targets BDNF mRNA, is up-regulated by MPP+ in SH-SY5Y cells. Importantly, inhibition of miR-210-3p prevents the reduction of BDNF production by MPP+ and improves the DA neuron survival in 1-methyl-4-phenyl-1,2,3,6-tetra hydropyridine (MPTP) model. Together, we demonstrated up-regulation of miR-210-3p by MPP+ reduces the BDNF production and contributes to the DA neuron damage.